Leg edema with (S)-amlodipine vs conventional amlodipine given in triple therapy for hypertension: a randomized double blind controlled clinical trial.

BACKGROUND: Leg edema is a common adverse effect of dihydropyridine Calcium Channel Blockers (CCB) that may need dose reduction or drug withdrawal, adversely affecting the antihypertensive efficacy. Leg edema is reported to occur less often with (S)-amlodipine compared to conventional racemic amlodipine. We aimed to find the incidence of leg edema as a primary outcome and antihypertensive efficacy with (S)-amlodipine compared to conventional amlodipine. METHODS: This prospective, double-blind, controlled clinical trial randomized 172 hypertensive patients, not controlled on beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), to either conventional amlodipine (5-10 mg; n = 86) or (S)-amlodipine (2.5-5 mg; n = 86), while continuing their previous anti-hypertensive medications. Sample was sufficient to find a difference in edema between the interventions with 80 % power at 5 % significance level. Intension to treat analysis (ITT) for safety data and per protocol analysis for efficacy data was performed. Fischer's exact test was applied to observe difference between responder rates and proportions of subjects having peripheral edema in the two groups. Pitting edema test scores were compared using Mann-Whitney test. RESULTS: Altogether 146 patients (amlodipine, n = 76 and (S)-amlodipine, n = 70) completed 120 days treatment. Demographic variables and treatment adherence were comparable in the two groups. Incidence of new edema after randomization was 31.40 % in test group and 46.51 % in control group [p = 0.03; absolute risk reduction (ARR) = 15.1 %; Number Needed to Treat (NNT) = 7, ITT analysis]. Pitting edema score and patient rated edema score increased significantly in the control compared to test group (p = 0.038 and 0.036 respectively) after treatment period. Edema scores increased significantly in the control group from baseline (p < 0.0001). Responders in blood pressure were 98.57 % in test and 98.68 % in control group. Most common adverse events (AE) were pitting edema and increased urinary frequency. Incidence of all AEs other than edema was similar in both groups. Two serious AEs occurred unrelated to therapy. Biochemical and ECG parameters in the two groups were comparable. CONCLUSIONS: In hypertensive patients not controlled on prior BB and ACEI/ARB therapy, addition of (S)-amlodipine besylate at half the dose of conventional amlodipine provides better tolerability with reduced incidence of peripheral edema, and equal antihypertensive efficacy compared to amlodipine given at usual doses. TRIAL REGISTRATION: Sri Lanka Clinical Trials registry: www.slctr.lk, SLCTR/2013/006.

High efficacy of bolus methylprednisolone in severe leptospirosis: a descriptive study in Sri Lanka.

BACKGROUND: In 2008, an outbreak of leptospirosis caused high mortality in Sri Lanka. The General Hospital, Peradeniya recorded nine deaths in May, which prompted the medical staff to change the treatment protocol. Addition of intravenous methylprednisolone (MP) to the treatment regimen of severely ill patients was implemented on the basis of immune mediated pathogenesis of the disease to reduce mortality. METHODS: The day MP commenced (25 May 2008), the study period was divided into a 'pre-MP period' and an 'MP period'. A clinical score ranging from 0-6 was applied to assess the severity of the infection. A score ≥2 was considered severe. Thus, 62 patients received bolus MP 500 mg intravenously for 3 days, followed by oral 8 mg for 5 days (MP given). Ten patients to whom MP was withheld were included in the MP period severe group (n=72). The same score was applied to pre-MP periods and 60 cases were identified as the historical control group (pre-MP period severe). RESULTS: There were 78 and 149 cases of leptospirosis in the pre-MP period and MP period, respectively. Of these cases, 17 and 16 patients died, with case death rates of 21.8% and 10.7%, respectively; the difference was significant (p=0.025). The survival rate at score 4 in the MP period severe group was 100% (16 of 16), compared to 38% (5 of 13) in pre-MP period severe group; this difference was highly significant (p<0.001). Six patients who died despite MP therapy had a clinical score of 5 or 6; four were alcohol consumers, and two had heart disease and hypertension. CONCLUSION: MP may reduce mortality in patients with severe leptospirosis, except in cases with established multiple organ dysfunction and comorbidities. Therefore, early administration of MP seems advisable.