Abstract

• Objective

The objective of this study was to compare the analgesic efficacy of etodolac injection and diclofenac injection in patients with postoperative orthopedic pain.

• Method

This was multicentric, randomized, assessor-blind and parallel-group study. A group of 158 patients with moderate to severe pain following orthopedic surgery were randomly assigned to receive either etodolac 400 mg twice a day (n=78) or diclofenac 75 mg thrice a day (n=80).

• Main outcome measures:

The primary efficacy outcome measures were pain intensity difference, sum of pain intensity differences and pain relief whereas secondary efficacy variables included maximum fall in pain intensity, number of doses of study medication consumed, number of patients who required rescue medication and overall response to therapy.

• Result

Mean pain intensity differences assessed on 10 cm VAS were significantly better for etodolac arm compared to diclofenac arm at 4, 8, 20 and 24 hours (p < 0.05). Sum of pain intensity differences over the first 8 hours (-21.31±6.26 for etodolac vs. -19.13±6.98 for diclofenac; p=0.041) and over the 24 hours (-39.83±10.70 for etodolac vs. -35.25±12.00 for diclofenac; p=0.012) for the etodolac group was significantly superior to diclofenac group. Assessment of pain relief showed that etodolac injection was significantly more effective than diclofenac injection (p < 0.0001) over the 24 hour assessment period. Maximum fall in pain intensity score, number of doses of study medication consumed and patients' and investigators' overall response to the drug at the end of treatment period were also significantly superior in the etodolac arm as compared to the diclofenac arm (p < 0.05). However, the number of patients who were rescued was comparable in both the treatment arms. A change in emotional functioning of the patients was not captured in this study. Both the study medications were well tolerated with no incidence of SAE throughout the study.

• Conclusion

Etodolac can be considered as an effective alternative to traditional NSAIDS in the treatment of post operative pain.

Abstract

• Objective

To demonstrate the clinical noninferiority of the analgesic effect of zaltoprofen (80 mg t.i.d.) compared with diclofenac (50 mg t.i.d.) in active knee osteoarthritis patients.

• Method

In this multicentric, double-blind, double-dummy, randomized, parallel-group, comparative study, 213 patients of either sex, aged 40 – 65 years having radiological and clinically confirmed primary knee osteoarthritis were randomized either to zaltoprofen (n = 105) or diclofenac (n = 108) and were followed-up at weeks 1, 2, 3 and 4. The treatment period was preceded by a washout period of 1 week.

• Results

Patients in both the zaltoprofen and diclofenac groups exhibited significant improvement (p < 0.001) in pain intensity, functional status and pain relief at each visit from baseline with no statistically significant difference between the two treatment groups. There was no statistically significant difference between the treatment groups for global assessment rating done by the patient and investigator at the end of therapy (p > 0.05) and the proportion of patients who consumed ranitidine (p = 0.135) and paracetamol (p = 0.086) tablets during the treatment period on both the treatment arms. Both the study medications were well tolerated with no incidence of serious adverse events.

• Conclusions

This study demonstrated that efficacy and safety of zaltoprofen is clinically noninferior to that of diclofenac.

• Abstract

The efficacy and safety of aceclofenac control release (CR) tablets was compared with conventional aceclofenac tablets in patients with knee osteoarthritis (OA). This was a double-blind, double- dummy, randomized, parallel group multicentric study conducted at 6 centers. Two hundred and eighty five patients were randomized to either aceclofenac-CR (n = 143) once daily or conventional aceclofenac tablet (n = 142) twice daily and were followed for 6 weeks. The efficacy parameters were pain intensity score on visual analogue scale, Western Ontario and McMaster (WOMAC) score, patients and investigator's overall study drug assessment and total consumption of acetaminophen and ranitidine tablets. Both treatments showed significant improvement in their efficacy parameters from baseline at the end of therapy. Aceclofenac-CR was comparable to conventional aceclofenac with respect to change in pain intensity and WOMAC score (P > .05) There was no statistically significant difference between the treatment groups in patient's and investigator's overall study drug assessment at the end of therapy (P > .05). Aceclofenac-CR treated patients took fewer acetaminophen and ranitidine tablets during the treatment period as compared to conventional aceclofenac treated patients. Both the study medications were well tolerated with no incidence of serious adverse event (SAE). In conclusion, the new aceclofenac-CR formulation was found to be effective and safe while offering practical advantage of once daily administration.

• Abstract

The objectives of this study were to evaluate the efficacy and tolerability of glimepiride plus extended release metformin on glycemic control in patients with Type 2 diabetes mellitus uncontrolled on monotherapy with sulfonylurea or metformin. This was a prospective, open labeled, multicentric study over 12 weeks. Patients who were diagnosed of Type 2 diabetes and were uncontrolled on monotherapy with single oral hypoglycemic agent like glimepiride or metformin and characterized by HbA1c  7% and ≤ 10% and FPG  140 mg/dl were enrolled in this study. Treatment regimen was started at 1mg glimepiride plus 500mg metformin once a day and was titrated to next dose level depending on the clinician's judgment, not exceeding total daily dose of 8mg glimepiride and 2000mg metformin. After 12-weeks treatment, glimepiride plus metformin combination showed improvement in metabolic control as assessed by changes in HbA1c, FPG & PPG. Primary efficacy parameter, HbA1c, was significantly reduced to (7.65±1.70) at the end of treatment from the baseline value (8.35±0.93) (P<0.001). 65.79% of patients showed  0.5% reduction in HbA1c and or HbA1c <7% at the end of therapy. FPG and PPG were significantly reduced at end of the therapy as compared to baseline values (p<0.001). Moreover, the lipid profile was also improved during the treatment period. The addition of glimepiride to metformin is an effective treatment for patients inadequately controlled on sulfonylurea or metformin alone. Combination of glimepiride with metformin achieves good glycemic control with better tolerability profile.

Abstract

• Objective

The objective of this study was to compare the effects of gliclazide/metformin on glycemic control in patients with Type 2 diabetes mellitus uncontrolled on monotherapy with sulfonylurea or metformin. This was a prospective, open-labeled, multicentric study over 12 weeks. Patients who were diagnosed of Type 2 diabetes and were uncontrolled on monotherapy with oral hypoglycemic agents, including gliclazide and metformin, characterized by HbA1c 7% or greater and 10% or less and fasting plasma glucose (FPG) 140 mg/dL or greater were enrolled in this study. The treatment regimen was started at 80 mg gliclazide plus 500 mg metformin once a day and was titrated to the next dose level depending on the clinician's judgment, not exceeding a total daily dose of 320 mg gliclazide and 2000 mg metformin. Changes from baseline HbA1c, FPG, and postprandial glucose were examined. After 12-weeks treatment, the gliclazide + metformin combination showed improvement in metabolic control as assessed by changes in HbA1c, FPG, and postprandial glucose. The primary efficacy parameter, HbA1c, was significantly reduced to 7.35 ± 1.10 at the end of treatment from the baseline value (8.51 ± 0.77) (P < 0.001). A total of 84.35% of patients showed a 0.5% or greater reduction in HbA1c and 37.39% of patients reported less than 7% HbA1c at the end of therapy. FPG and postprandial glucose were significantly reduced at the end of therapy as compared with baseline values (P < 0.001). Moreover, the lipid profile was also improved during the treatment period. The addition of gliclazide to metformin is an effective treatment for patients inadequately controlled on sulfonylurea or metformin alone. A combination of gliclazide with metformin achieves good glycemic control and improves lipid levels with better tolerability profile.

Abstract

• Background

Epidemiological studies and clinical trials have shown that prevention of cardiovascular disease, the ultimate goal of hypertension treatment, requires a sufficient reduction in blood pressure.

• Objective

The primary objective of this study was to compare the mean decrease in systolic (SBP) and diastolic (DBP) blood pressure between metoprolol extended release (XL)/amlodipine fixed-dose combination and losartan plus amlodipine combination in patients with mild-to-moderate essential hypertension. The secondary objectives of this study were to compare the proportion of responders in the two treatment groups and to evaluate the tolerability of the study medications.

• Methods

This was a randomized, parallel-group, multicentre comparative study conducted at the outpatient departments of three teaching hospitals in India. Patients with mild-to-moderate hypertension (defined as DBP 90-109 mmHg) aged between 18 and 75 years were enrolled in this study and followed up for 12 weeks. Response to study treatments was evaluated in terms of mean decrease in SBP and DBP and the response rate (reduction to SBP <140 mmHg and DBP <90 mmHg).

• Main outcome measures

Clinical assessment was done at screening, randomization, and at 2 weeks, 4 weeks and 8 weeks of treatment by calculating Western Ontario MacMaster (WOMAC) scores, time taken to walk 100 feet, visual analogue scores for pain, investigator's assessment on a Likert scale and joint tenderness. Tolerability assessment was based on adverse events. Patients compliance was also assessed.

• Result

Out of 152 patients who underwent a 1-week placebo washout, 148 eligible patients were randomized to receive either metoprolol XL 25 mg/amlodipine 2.5 mg fixed-dose combination (76 patients) or losartan 25 mg plus amlodipine 2.5 mg (72 patients). The two treatment groups were similar with respect to demographic and baseline characteristics. Non-responders after 4 weeks of therapy were escalated to metoprolol XL 50 mg/amlodipine 5 mg fixed-dose combination or losartan 50 mg plus amlodipine 5 mg, respectively. The study was completed by 66 patients in each group, of whom 43 patients in each group responded to the starting doses. After 4 weeks' therapy, both treatments were associated with significant decreases in SBP and DBP from baseline (p < 0.001) and were comparable with respect to mean decrease in SBP (p = 0.304), mean decrease in DBP (p = 0.630) and response rate (p = 1.0). Also, both the step-up therapies were comparable with respect to mean decrease in SBP (p = 0.484), mean decrease in DBP (p = 0.650) and response rate (p = 0.134) at week 12. Both treatments were well tolerated in the studied population.

• Conclusion

Metoprolol XL/amlodipine fixed-dose combination was found to be as effective and well tolerated as losartan plus amlodipine in the treatment of essential hypertension.

Abstract

• Objective

To evaluate the efficacy and safety of etodolac-paracetamol combination in comparison with etodolac alone in patients with knee osteoarthritis (OA) flare-up.

• Methods

In this double-blind, double-dummy, randomized, comparative, multicentric, parallel group study, 220 patients of either sex in the age range of 40 to 70 years with an OA flare-up were randomized either to etodolac (300 mg)-paracetamol (500 mg) combination or etodolac (300 mg) alone twice a day for 10 days. Efficacy outcomes were an average daily pain intensity score on 11-point visual analog scale, Western Ontario and McMaster score (WOMAC), and Lequesne Severity Index; total pain relief score at 30 minutes, 1, 2, and 4 hours after first-dose administration; OA flare-up symptoms resolution; patient's and investigator's overall assessment of study treatments.

• Result

Etodolac-paracetamol was significantly superior to etodolac alone in reducing pain intensity (P<0.001), achieving pain relief (P <0.05) during the first 4 hours after the study dose administration, and resolution of the clinical signs and symptoms of OA flare-up such as morning stiffness, swelling/inflammation, and erythema. The combination showed significantly greater improvement in WOMAC scores and Lequesne Severity Index (P<0.001) than in etodolac monotherapy. Peak pain intensity difference over a period of 10 days was also significantly (P<0.001) higher in combination-treated patients compared with monotherapy-treated patients. The combination had significantly better patient's and investigator's global efficacy assessment (P=0.001). Both treatments were well tolerated and safe in patients with OA flare-up.

• Conclusion

For the treatment of painful OA flare-ups, the etodolac-paracetamol combination can offer improved clinical outcomes by targeting multiple pain pathways. The results of the current study show that etodolac-paracetamol is more effective in the treatment of OA flare-up than etodolac alone.

Abstract

• Objective

To evaluate the efficacy and safety of aceclofenac-drotaverine combination against aceclofenac alone in patients with primary dysmenorrhoea.

• Study Design

This double-blind, double-dummy, randomized, comparative, multicentric study enrolled 200 women (100 women in each arm) in the age range of 18-35 years with primary dysmenorrhoea at four centers. The patients were randomly allocated to either aceclofenac 100mg-drotaverine 80 mg b.i.d or aceclofenac 100mg alone b.i.d for a maximum of 3 days. Primary efficacy parameters were total area under pain relief (PR) score up to 4 and 8h (TOPAR/4 and TOPAR/8). Secondary efficacy measurements were pain-intensity difference (PID), sum of PID over 4 and 8h (SPID/4 and SPID/8), peak PID over 4 and 8h and peak PR over 4 and 8h, total study drug consumption, and patient's and investigator's global evaluation of the efficacy.

• Result

Both treatments showed significant improvement in baseline values in all efficacy parameters. The combination was significantly superior to monotherapy in terms of TOPAR/4 (24.0 vs 18.54) (p=0.000) and TOPAR/8 (40.3 vs 35.2) (p=0.003), SPID/4 (-17.9 vs -13.88) (p=0.000) and SPID/8 (-31.06 vs -26.8) (p=0.001), peak PID/4 (-6.60 vs -5.75) (p=0.001) and peak PR/4 (8.26 vs 7.10) (p=0.000). At the end of 8h, both treatments were comparable with respect to peak PID/8 and peak PR/8 (p>0.05). The total number of doses consumed by patients treated with combination therapy was less than with monotherapy (150 vs 168 doses). The combination was significantly superior to monotherapy with respect to patient's and investigator's global evaluation of the efficacy (p=0.002 and p=0.001, respectively). Both treatments were well tolerated.

• Conclusion

This study establishes the efficacy of aceclofenac-drotaverine combination in patients with primary dysmenorrhoea. The fixed-dose combination of aceclofenac and drotaverine should therefore be considered as a suitable, effective and well tolerated treatment option for primary dysmenorrhoea.

Abstract

As there is a strong, positive, and continuous correlation between blood pressure and risk of cardiovascular diseases; improved control of blood pressure is necessary to product maximum reduction in clinical cardiovascular endpoints. The primary objective was to demonstrate that atenolol/amlodipine combination thereapy is superior to atenolol monotheray with respect to mean fall in systolic blood pressure and diastolic blood pressure. The secondary objective was to compare the response rate and to evaluate the tolerability of study medications. This randomized, comparative, multicentric, 12-week study consisted of screening visit followed by baseline visit 48-hours postscreening. All enrolled patients received 7-day pacebo washout. Eligible patients were randomized to receive either atenolol 25mg/amlodipine 2.5 mg or atenolol 25 mg alone. Nonresponders after 4 weeks of therapy were escalated to atenolol 50 mg/amlodipine 5 mg or atenolol 50 mg, respectively. Out of 190 enrolled patients (94: combination group; 96: monotherapy group), 174 patients (84: combination therapy; 90: monothereapy) completed the study. After 4 weeks of therapy, low-dose combination group was superior to low-dose monotherapy with respect to mean fall in SBP (P=0.008) and DBP (P=0.021) and response rate (P=0.012). Also high-dose combination therapy was superior to high-dose monotherapy with respect to mean SBP (P=0.001), DBP (P= 0.011), and response rate (P= 0.035) at the end of 12 weeks of therapy. At the end of therapy, significantly more number of patients from combination group achieved normalization of BP (SBP< 120 mmHg and DBP <80 mmHg) (P= 0.009). Thus, once daily treatment with atenolol/amlodipine fixed-dose combination offers superior antihypertensive efficacy over atenolol monotherapy in patients with mild-to-moderate essential hypertension.

Abstract

• Objective

High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-to-moderate essential hypertension.

• Method

Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.

• Result

The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorithalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (NA⁺, K⁺, CL-) and fasting blood sugar, evident across the treatment groups.

• Conclusion

Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.

Abstract

• Objective

The relationship of blood pressure (BP) to cardiovascular risk is linear, positive, and continuous. Lowering elevated BP reduces the risk of cardiovascular events. The primary objective of this randomized, multicenter, comparative, 3-month, open-label study was to evaluate the antihypertensive efficacy of losartan/chlorthalidone versus losartan/ hydrochlorothiazid in mild-to-moderate essential hypertension.

• Method

A total of 137 eligible patients underwent a 2-week placebo washout period, following which 131 patients were randomized to losartan (L) 25 mg/chlorthalidone (C) 6.25 mg (66/131) or to losartan 25 mg/hydrochlorothiazide (H) 12.5 mg (65/131) at three centers. Patients not responding after 4 weeks of therapy were escalated to losartan 25 mg/chlorthalidone 12.5 mg and losartan 50 mg/hydrochlorothiazide 12.5 mg, respectively.

• Result

Both treatment groups were similar with respect to demography and baseline characteristics. Altogether, 120 patients completed the study. After 4 weeks of therapy, both treatments showed a significant fall from baseline in systolic BP (SBP) and diastolic BP (DBP) (L/C:-20.17/-10.30; L/H:-17.63/-10.20). Both treatments were similar with respect to mean fall in SBP (p=0.258), DBP (p=0.934) and response rate (p=0.769). Both step-up therapies were similar with respect to mean fall in SBP (p=0.418), DBP (p=0.389) from baseline and response rate (p= 0.769). All reported adverse events were of mild-to-moderate intensity, except for two serious AEs that occurred in patients who received L/H.

• Conclusion

The losartan/low-dose chlorthalidone (6.25mg) combination is as effective as the widely used losartan/hydrochlorothiazide combination in lowering BP and is well tolerated, thus providing a useful therapeutic option for treating mild-to-moderate hypertension.

Abstract

Tizanidine and aceclofenac individually have shown efficacy in the treatment of low back pain. The efficacy and tolerability of the combination have not yet been established. The objective of the study was to evaluate the efficacy and safety of Aceclofenac-tizanidine fixed dose combination against aceclofenac alone in patients with acute low back pain. This double-blind, double-dummy, randomized, comparative, multicentric, parallel group study enrolled 197 patients of either sex in the age range of 18-70 years with acute low back pain. The patients were randomized to receive either Aceclofenac (100 mg) - tizanidine (2mg) b.i.d or aceclofenac (100 mg) alone b.i.d. for 7 days. The primary efficacy outcoems were pain intensity (on movement, at rest and at night; on VAS scale) and pain relief (on a 5-point verbal rating scale). The secondary efficacy outcomes measures included functional impairment (modified Schober's test and lateral body bending test) and patient's and investigator's global efficacy assessment. Aceclofenac-tizanidine was significantly superior to aceclofenac for pain intensity (on movement, at rest and at night; P <0.05) and pain relief (P=0.00) on days 3 and 7. There was significant increase in spinal flexion in both the groups from baseline on days 3 and 7 with significant difference in favour of the combination group (P<0.05). There were significantly more number of patients with excellent to good response for the Aceclofenac-tizanidine treatment as compared to aceclofenac alone (P=0.00). Both the treatments were well tolerated. In this study, Aceclofenac-tizanidine combination was more effective than aceclofenac alone and had a favourable safety profile in the treatment of acute low back pain.

Abstract

• Objective

To evaluate efficacy and safety of aceclofenac-paracetamol combination against aceclofenac alone in patients with osteoarthritis (OA) flare-up.

• Method

This open, randomized, comparative, multicentric, 10-day study enrolled 199 patients (aceclofenac 100 mg + paracetamol 500 mg bid: 101; aceclofenac 100 mg, bid: 98) with painful OA flare-up. Primary efficacy parameters were pain intensity difference (PID), sum of PID (SPID), and peak PID over 4 h (0.5, 1, 2, 4 h) after first dose of study medication. Secondary efficacy measurements were mean pain intensity scores from day 1 to day 10, WOMAC scores, changes in baseline signs and symptoms, and patient's and investigator's overall efficacy assessment.

• Result

Both treatments showed significant improvement in their baseline values in all efficacy parameters. The combination was superior over monotherapy in terms of PID (-0.54 vs -0.23, -1.23 vs -0.72, -1.73 vs -1.23 and -1.94 vs -1.43 at 0.5, 1, 2 and 4 h respectively), SPID (-5.46 vs -3.63) and peak PID (-2.08 vs -1.56; p <0.05). At the end of therapy, both treatments were comparable (p > 0.05) with respect to average pain intensity from day 1 to day 10, changes in WOMAC scores and resolution of baseline signs and symptoms. The combination was significantly superior to monotherapy with respect to the patients' and investigators' overall efficacy assessments (p = 0.035 and p = 0.009 respectively).

• Conclusion

The findings of this open-label, comparative study in Indian patients demonstrates that aceclofenac-paracetamol combination is effective and well tolerated in relieving OA flare-up pain. The combination showed rapid pain relief compared with monotherapy which is desirable by such patients and, hence, this combination can play an important role in the management of acute painful OA flare-up.

Abstract

• Objective

Beta-lactamase producing bacteria present a major problem in treating lower respiratory tract infections. The objective of this study was to evaluate efficacy and safety of cefotaxime-sulbactam combination versus amoxicillin-clavulanic acid injection as an alternative therapeutic option for treatment of lower respiratory tract infections in pediatric patients.

• Method

This randomized, multicentric, comparative study enrolled 102 in-patients with lower respiratory tract infections, in the age range of 3 months - 12 years. Patients received cefotaxime-sulbactum or amoxicillin-clavulanic acid injection intravenously for up to 7 days.

• Result

There was no difference between the two groups in demography or disease characteristics (p > 0.05) at baseline. Efficacy was evaluated in a total of 96 patients. Both the treatment groups were comparable in response rate at the end of the therapy (p > 0.05). Clinical success rate was 93.6% and 89.8%, respectively for cefotaxime-sulbactum and co-amoxiclav. One patient from the cefotaxime-sulbactum group reported convulsions, which were probably not related to the study medication in the opinion of the investigator. Except for this serious adverse event, both the study medications were safe and well tolerated in the study population.

• Conclusion

In conclusion, cefotaxime-sulbactam administered 3 times a day for up to 7 days was found to be as effective as co-amoxiclav therapy. However, further studies with a large number of patients are required to confirm these findings with more robust microbiological evaluation.

Abstract

This randomized, multicentre, comparative study evaluated the efficacy and safety of treatment with cefuroxime-sulbactam compared with amoxicillin-clavulanic acid (co-amoxiclav) in patients with lower respiratory tract infections (LRTIs). The study enrolled 75 adult in-patients with moderate to severe LRTIs. Patients were treated intravenously for 7-10 days. The treatment groups were comparable at baseline with respect to demographic and disease characteristics. Efficacy was evaluated in 72 patients. The clinical success rate was statistically superior in-patients treated with cefuroxime-sulbactam (100%) compared with patients treated with amoxicillin-clavulanic acid (88%). The bacteriological success rate was 95% and 100% for cefuroxime-sulbactam and amoxicillin-clavulanic acid, respectively, with no significant difference between treatments. Both treatments were safe and well tolerated. One patient in the cefuroxime-sulbactam group reported convulsions, which the investigator considered were probably not related to the study medication. Cefuroxime-sulbactam can be an effective alternative empirical treatement for LRTIs.

Abstract

• Objective

To compare the efficacy and safety of low-dose chlorthalidone + atenolol combination with atenolol and atenolol + amlodipine combination in stage I hypertensive patients uncontrolled on active run-in monotherapy.

• Method

Newly diagnosed stage I hypertensive patients were randomized to active run-in monotherapy either with atenolol 25 mg (98/300) or chlorthalidone 6.25 mg (100/300) or amlodipine 2.5 mg (102/300). A total of 282/300 patients (atenolol 92, chlorthalidone 91, amlodipine 99) completed the active run-in phase successfully. Patients uncontrolled on active run-in monotherapy (atenolol 33, chlorthalidone 45, amlodipine 47) received the study treatment, namely atenolol 50 mg alone, chlorthalidone 6.25 mg + atenolol 25 mg and atenolol 25 mg + amlodipine 2.5 mg, respectively. Efficacy of the therapy was evaluated by BP measurement at weeks 12 and 20 post-therapy.

• Result

Post-active run-in monotherapies, the study treatment groups showed a significant fall in mean SBP and DBP from baseline (p < 0.05). The mean fall in SBP and DBP was comparable for study treatments (atenolol 50 mg, atenolol 25 mg + chlorthalidone 6.25 mg and atenolol 25 mg + amlodipine 2.5 mg) (p=0.337 for SBP and p=0.054 for DBP) at week 12 and (p=0.744 for SBP and p=0.855 for DBP) at week 20; also, the percentage of responders was comparable for the three study treatment groups (p=0.799) indicating that the low-dose chlorthalidone + atenolol combination is non inferior to the high-dose atenolol alone and atenolol + amlodipine combination. No serious laboratory/clinical adverse events were reported in this study.

• Conclusion

Chlorthalidone 6.25 mg in combination with atenolol 25 mg is effective and safe in stage I (JNC 7) essential hypertensive patients. This low dose of chlorthalidone could reduce dose-related concerns over metabolic adverse effects and may lead to wider usage of this proven antihypertensive agent in combination therapy.

Abstract

• Objective

Polymorphic light eruption is the most common photodermatosis charaterized by nonscarring, pruritic, erythematous papules and plaques.

• Aim

To evaluate the efficacy and safety of hydroxychloroquine in comparison with chloroquine in patients suffering from polymorphic light eruption.

• Method

This was a randomized, double-blind, comparative, multicentric study conducted at two centers. This study enrolled 68 (58.1%) males, 49 (41.8%) females whose ages ranged from 18-73 years and average weight was 57.89 ± 8.27 kg. A total of 117 patients were enrolled in the study. Out of 117 patients, 63 patients were randomized to receive hydroxychloroquine tablets 200 mg twice daily for the first month and 200 mg once daily for the next month. Similarly, 54 patients were randomized to receive chloroquine tablets 250 mg twice daily for the first month and 250 mg once daily for the next month. The total duration of therapy for both the study arms was two months. The severity and frequency of burning, itching, erythema and scaling were evaluated at predetermined intervals (at baseline, after four, eight and 12 weeks of therapy).

• Result

A significant reduction in severity scores for burning, itching, and erythema was observed in patients treated with hydroxychloroquine than with chloroquine (P < 0.05). However, hydroxychloroquine was as good as chloroquine in reducing severity of scaling at the end of the study evaluation ( P = 0.229). The good to excellent response was reported by 68.9% of the patients who received hydroxychloroquine and by 63% of the patients who received chloroquine. The adverse events reported were mild to moderate and none of the patients reported any serious adverse events or ocular toxicity in this study.

• Conclusion

Hydroxychloroquine was found to be significantly more effective than chloroquine in the treatment of polymorphic light eruption and can be used safely in the dosage studied in such patients with little risk of ocular toxicity.

Abstract

• Objective

Hydroxychloroquine (HCQ) has been used for a long time worldwide as a therapy for rheumatoid arthritis (RA). This trial was designed to determine whether HCQ was efficacious and safe in Indian Patients with RA.

• Research design and Method

The trial was a multicentre, placebo controlled, randomized and double-blind study . One hundred and twenty-two patients with RA were enrolled in 3 different centres for the trial (26 males and 96 females in the age group of 18-60 years). Patients were randomized to receive either hydroxychloroquine tablets (n = 61) two tablets of 200mg daily or placebo (n = 61) two tablets daily. After 8 weeks all patients received one tablet of hydroxychloroquine 200mg daily for 4 weeks. Every patient also received one tablet of Nimesulide 100mg twice daily.

• Main outcome measures

Assessment of response at 12 weeks using modified ACR 20 (American College of Rheumatology 20) criteria where Health Assessment Questionnaire (HAQ) was replaced by ARA (American Rheumatology Association) functional class.

• Result

40.4% of patients on hydroxychloroquine showed improvement by modified ACR response criteria whereas only 20.7% (p = 0.02) showed improvement in the placebo group. No significant side effects were observed in any of the patients. There were no ocular toxicities.

• Conclusion

Hydroxychloroquine was found to be an effective and well-tolerated drug in rheumatoid arthritis in Indian patients.

One hundred thirty-eight adult patients with acute Plasmodium falciparum malaria were randomized to receive either β-arteether or α/β-arteether. The drugs were administered in the dose of 150 mg once a day intramuscularly for three consecutive days in hospitalized patients. After one week of hospitalization, patients were followed-up for three weeks after release from the hospital. There was no statistically significant difference between cure rates, mean fever clearance time (FCT), mean parasite clearance time (PCT), and occurence of side effects in either group. The cure rate was 97.14% for β-arteether and 97.01 for α/β-arteether (P = 0.9660). The mean PCT was 38.49 hours for β-arteether and 36.90 hours for α/β-arteether (P = 0.6054), and the mean FCT was 37.27 hours for β-arteether and 37.9 hours for α/β-arteether (P = 0.8718). Both arteether formulations were safe and efficacious in reducing the clinical symptoms of acute falciparum malaria. There was also rapid clearance of parasitemia with both formulations. Thus, either β-arteether or α/β-arteether can be used in the treatment of acute falciparum malaria.

• Objective

Osteoarthritis is one of the most common forms of arthritis seen in primary care. Non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the management of osteoarthritis. However, gastrointestinal (GI) side effects limit their use. Cyclooxygenase-2 (COX-2) selective inhibitors exhibit better GI tolerability than conventional NSAIDs, but their cardiovascular safety is controversial. An NSAID with high efficacy, high GI tolerability and devoid of adverse cardiovascular effects is therefore a profile preferred by physicians. Aceclofenac is an anti-inflammatory and analgesic drug with preferential COX-2 inhibition. The objective of this study was to assess the efficacy and safety of aceclofenac in the treatment of osteoarthritis in an Indian population.

• Research design and Method

The trial was controlled, comparative, randomized, and double-blind. The study included 247 patients (82 males and 165 females, 40-82 years), suffering from osteoarthritis. Patients were randomized to receive either aceclofenac (100 mg twice daily) or diclofenac (75 mg twice daily).

• Main outcome measures

Clinical assessment was done at screening, randomization, and at 2 weeks, 4 weeks and 8 weeks of treatment by calculating Western Ontario MacMaster (WOMAC) scores, time taken to walk 100 feet, visual analogue scores for pain, investigator's assessment on a Likert scale and joint tenderness. Tolerability assessment was based on adverse events. Patients compliance was also assessed.

• Result

Aceclofenac was found to be statistically superior to diclofenac in efficacy parameters of WOMAC scores, investigator's assessment and joint tenderness. Aceclofenac was found to be statistically superior to diclofenac in terms of epigastric discomfort, dyspepsia and abdominal pain. Compliance was also better with aceclofenac. The overall response of patients' osteoarthritis to aceclofenac was found to be statistically superior to diclofenac by both physician and patient.

• Conclusion

Aceclofenac is an effective and well-tolerated drug in osteoarthritis in the Indian setting.