Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group.

BACKGROUND: The effects of oral rehydration solution (ORS) with reduced osmolarity on children with acute watery diarrhoea are known, but little is known about the effects of such ORS on adults with cholera. We aimed to compare the efficacy and safety of an ORS with reduced osmolarity with that of standard WHO ORS in adults with cholera. METHODS: We undertook a double-blind, controlled clinical trial in adults with severe cholera at the International Centre for Diarrhoeal Disease Research, Bangladesh. Our primary outcomes were mean stool output in the 24 h after randomisation, proportion of patients who needed unscheduled intravenous therapy, and proportion of patients with biochemical hyponatraemia 24 h after randomisation. FINDINGS: 147 patients received ORS with reduced osmolarity and 153 received standard WHO ORS. There was no significant difference between the two groups in terms of main outcome variables: mean initial 24 h and total stool output (reduced osmolarity vs standard WHO ORS 212 [SE 8] vs 207 [8] and 284 [13] vs 273 [13] g/kg respectively), duration of diarrhoea (46 [1.5] vs 43 [1.5]). The proportion of patients vomiting during the first 24 h and the proportion who received unscheduled intravenous infusion during the first 24 h was similar between groups. More patients on reduced osmolarity ORS than on standard WHO ORS developed hyponatraemia during the first 24 h, defined as serum sodium concentration below 130 mmol/L (29 of 142 vs 16 of 150; odds ratio 2.1 [95% CI 1.1-4.1]). However, all hyponatraemic patients in both groups were symptom-free and the proportion of patients with serum sodium concentration below 125 mmol/L was similar between groups. INTERPRETATION: There was no difference in clinical outcome between cholera patients treated with reduced osmolarity ORS solution and those treated with standard WHO ORS. The risk of increased incidence of symptom-free hyponatraemia in patients with cholera treated with an ORS with reduced osmolarity should be further assessed by meta-analysis. The risk should be taken into account when choice of ORS is made in areas in which cholera is endemic.

Sacolene in cholera: a double blind randomized controlled trial.

Methylated casein (Sacolene), a diarrhoea remedy used in Europe, has shown an antisecretory effect in cholera-induced secretion in animals and benefit in diarrhoea in humans. In this placebo controlled trial Sacolene was evaluated in 78 male adults with severe cholera who, after initial i.v. therapy received Sacolene or placebo, 4 g at start and 2 g 4 hourly until cessation of diarrhoea, along with oral rehydration therapy and repeat i.v. therapy if indicated. No antibiotics were given during the study. The purging rate and diarrhoea duration were similar in the 2 groups. The proportion of patients requiring repeat courses of i.v. therapy in the study group was 46% compared with 69% in controls (i.e. reduced by 23%, p = 0.04). While the severity of purging was not reduced, the proportion of patients requiring repeat i.v. therapy was reduced by Sacolene therapy. The latter finding may indicate some benefit from Sacolene in cholera, though this requires confirmation.