Original article—alimentary tract
Oral Diosmectite Reduces Stool Output and Diarrhea Duration in Children With Acute Watery Diarrhea

https://doi.org/10.1016/j.cgh.2008.12.007Get rights and content

Background & Aims

Diosmectite is a clay used to treat children with acute watery diarrhea. However, its effects on stool output reduction, the key outcome for pediatric antidiarrheal drugs, have not been shown.

Methods

Two parallel, double-blind studies of diosmectite efficacy on stool reduction were conducted in children 1 to 36 months old in Peru (n = 300) and Malaysia (n = 302). Inclusion criteria included 3 or more watery stools per day for less than 72 hours and weight/height ratios of 0.8 or greater. Exclusion criteria were the need for intravenous rehydration, gross blood in stools, fever higher than 39°C, or current treatment with antidiarrheal or antibiotic medications. Rotavirus status was determined. Diosmectite dosage was 6 g/day (children 1–12 months old) or 12 g/day (children 13–36 months old), given for at least 3 days, followed by half doses until complete recovery. Patients were assigned randomly to groups given diosmectite or placebo, in addition to oral rehydration solution (World Health Organization).

Results

Children in each study had comparable average ages and weights. The frequencies of rotavirus infection were 22% in Peru and 12% in Malaysia. Similar amounts of oral rehydration solution were given to children in the diosmectite and placebo groups. Stool output was decreased significantly by diosmectite in both studies, especially among rotavirus-positive children. In pooled data, children had a mean stool output of 94.5 ± 74.4 g/kg of body weight in the diosmectite group versus 104.1 ± 94.2 g/kg in the placebo group (P = .002). Diarrhea duration was reduced by diosmectite, which was well tolerated.

Conclusions

These results show that diosmectite significantly decreased stool output in children with acute watery diarrhea, especially those who were rotavirus-positive.

Section snippets

Subjects

The Peru and Malaysia studies included children with acute watery diarrhea, in primary care hospitals.

According to previous studies it was expected that the decrease of total 72-hour stool output would be 30 g/kg of bodyweight with active drug compared with placebo, with a common standard deviation (SD) of 80 g/kg. For rejection of a 2-sided null hypothesis with a type I error of 5% and a type II error of 20%, at least 112 patients had to be included per group. We decided to include 300

Study populations

Three hundred patients were included in the intent-to-treat population (153 in the placebo group and 147 in the diosmectite group) between June 23, 2006, and February 1, 2007, in 11 primary care hospitals located in Lima (n = 9), Huacho (n = 1), and Ica (n = 1). Seventy-eight major deviations to the protocol were observed in 40 patients: 5 inclusion criteria were not respected, 39 patients were hospitalized for fewer than 70 hours, and 34 had treatment exposure for less than 48 hours. The

Discussion

The present studies show that diosmectite, used as an adjunct therapy to the ORS currently recommended by the World Health Organization,4 decreased 72-hour stool output in children, particularly if rotavirus-positive, and shortened the duration of acute watery diarrhea.

This study shows a significant effect of diosmectite on stool output, studied as a primary outcome, and diarrhea duration.7, 10, 11, 12, 13, 14, 21 In a previous study, Madkour et al13 showed that diosmectite shortens diarrhea

Acknowledgments

The authors are grateful to the nurses and study monitors who greatly helped with the patients in the study, to the Clinical Research Center (CRC), Kuala Lumpur Hospital, for monitoring in Malaysia, to Dr Elisabeth Leger-Picherit who performed the statistical analysis, and to Dr Guillaume Hébert from SC Partners who assisted in preparing the manuscript.

The Peru Diosmectite Study Group: Dante Figueroa Quintanilla, Pablo Huamaní Echeccaya: Instituto Especializado de Salud del Niño, Lima, Peru;

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    Conflicts of interest Hélène Mathiex-Fortunet and Philippe Garnier are Ipsen employees.

    Christophe Dupont, Jimmy Lee Kok Foo, Nicholas Moore, and Eduardo Salazar-Lindo have received honoraria and/or compensation in regards to the study, as an investigator, coordinator, or expert, in relation with the time spent on the study. The authors declare no conflict of interest in regards to the present article derived from the study, for which no compensation or stipend was received. There is no organic or regular relationship between the authors and Ipsen. The authors own no shares in Ipsen and no member of their immediate family is employed by Ipsen. Guillaume Hébert, from SC Partners, assisted in preparing the manuscript, according to a contract between Ipsen and SC Partners. The sponsor participated in study design, choice and set-up of centers, training for standardized stool collection, providing of materials (scales, diapers, World Health Organization oral rehydration solution), data monitoring, data collection, and preparation of the clinical study report.

    Funding This study was supported by Ipsen, France, the developer of diosmectite and the owner of Smecta.

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