Racecadotril in Acute Diarrhea
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《交互式心脏血管和胸部手术》
Department of Paediatric Gastroenterology and Nutrition, Robert Debre Hospital, Paris, France.
A recent editorial review [1] concisely yet comprehensively summarizes the main properties and advantages of racecadotril, the first purely intestinal antisecretory drug. Nevertheless, some points raised by the author need clarification.
The results of a study by Cezard, et al. were questioned because (1) "collection of stool uncontaminated by urine is difficult in girls", (2) a larger number of patients were withdrawn from the racecadotril group for trial deviation. In fact (a) this study was conducted in a University Hospital Center greatly experienced in infant stool collection, (b) both, boys and girls, were treated and the sex ratio was similar in the placebo group, (c) patient withdrawal had no statistical consequence since "intention-to-treat" and "per-protocol" analysis led to similar results.
The opinion that "There was no study to evaluate adverse effect - possibly rebound - after the drug has been discontinued" should be revised: in several studies, monitoring for adverse effects was conducted for 5-10 days whereas diarrhoea (and therefore treatment) lasted 2-3 days and no rebound or adverse effect were reported.
The concern about a multi center trial for which "we are unable to locate a publication discussing the results"[1] can be addressed. The study was conducted by a multinational company distinct from the French company in which the drug was discovered and developed and its design allowed to assess safety rather than efficacy of racecadotril. Thus, whereas the former studies were performed in a limited number of centres in a single country, during a single period, i.e., under conditions likely to ensure homogeneity in geographical and epidemiological terms, the study in question was performed in 24 centers from 16 different countries scattered in Latin America and Asia, each center providing a small number of cases. Hence, the design and the inherently difficult monitoring of the study led to a large number of missing data and heterogeneity of available ones. These drawbacks did not allow publication of the study in a decent journal. Nevertheless, the study was provided to health authorities and was considered as a safety study (excellent on this parameter).
As a conclusion, we would like to mention that a number of expert groups have recently underlined the interest of racecadotril in the management of acute diarrhea(2-5).
References
1. Bhan MK. Racecadotril. Is There Enough Evidence to Recommend it for Treatment of Acute Diarrhea Editorial. Indian Pediatrics 2004; 41: 1203-1204.
2. Canadian Pediatric Society. Treatment of diarrhoeal diseases. Position statement. Pediatrics & Child Health 2003;8:455-458 and 463-466.
3. Cézard JP, Chouraqui JP, Girardet JP, Gottrand F, et le Groupe Francophone d’Hépatologie, Gastroentérologie et Nutrition Pédiatriques. Traitement médicamenteux des diarrhées aigus infectieuses du nourrisson et de l'enfant. Arch Péd 2002, 9 :620-628.
4. Centers for Disease Control and Prevention. Managing acute gastroenteritis among children. Oral rehydration, maintenance, and nutritional therapy. MMWR 2003;52 (N° : RR16).
5. Manatsathit S, DuPont HL, Farthing M, Kosit-chaiwat C, Leelakusolvong S, Rama-krishna BS, Sabra A, Speelman P, Surangsrirat S. Guideline for the management of acute diarrhea in adults. J Gastroenterol Hepatol 2002;17: S54-S71.(J.P. Cezard, E. Salazar-L)
A recent editorial review [1] concisely yet comprehensively summarizes the main properties and advantages of racecadotril, the first purely intestinal antisecretory drug. Nevertheless, some points raised by the author need clarification.
The results of a study by Cezard, et al. were questioned because (1) "collection of stool uncontaminated by urine is difficult in girls", (2) a larger number of patients were withdrawn from the racecadotril group for trial deviation. In fact (a) this study was conducted in a University Hospital Center greatly experienced in infant stool collection, (b) both, boys and girls, were treated and the sex ratio was similar in the placebo group, (c) patient withdrawal had no statistical consequence since "intention-to-treat" and "per-protocol" analysis led to similar results.
The opinion that "There was no study to evaluate adverse effect - possibly rebound - after the drug has been discontinued" should be revised: in several studies, monitoring for adverse effects was conducted for 5-10 days whereas diarrhoea (and therefore treatment) lasted 2-3 days and no rebound or adverse effect were reported.
The concern about a multi center trial for which "we are unable to locate a publication discussing the results"[1] can be addressed. The study was conducted by a multinational company distinct from the French company in which the drug was discovered and developed and its design allowed to assess safety rather than efficacy of racecadotril. Thus, whereas the former studies were performed in a limited number of centres in a single country, during a single period, i.e., under conditions likely to ensure homogeneity in geographical and epidemiological terms, the study in question was performed in 24 centers from 16 different countries scattered in Latin America and Asia, each center providing a small number of cases. Hence, the design and the inherently difficult monitoring of the study led to a large number of missing data and heterogeneity of available ones. These drawbacks did not allow publication of the study in a decent journal. Nevertheless, the study was provided to health authorities and was considered as a safety study (excellent on this parameter).
As a conclusion, we would like to mention that a number of expert groups have recently underlined the interest of racecadotril in the management of acute diarrhea(2-5).
References
1. Bhan MK. Racecadotril. Is There Enough Evidence to Recommend it for Treatment of Acute Diarrhea Editorial. Indian Pediatrics 2004; 41: 1203-1204.
2. Canadian Pediatric Society. Treatment of diarrhoeal diseases. Position statement. Pediatrics & Child Health 2003;8:455-458 and 463-466.
3. Cézard JP, Chouraqui JP, Girardet JP, Gottrand F, et le Groupe Francophone d’Hépatologie, Gastroentérologie et Nutrition Pédiatriques. Traitement médicamenteux des diarrhées aigus infectieuses du nourrisson et de l'enfant. Arch Péd 2002, 9 :620-628.
4. Centers for Disease Control and Prevention. Managing acute gastroenteritis among children. Oral rehydration, maintenance, and nutritional therapy. MMWR 2003;52 (N° : RR16).
5. Manatsathit S, DuPont HL, Farthing M, Kosit-chaiwat C, Leelakusolvong S, Rama-krishna BS, Sabra A, Speelman P, Surangsrirat S. Guideline for the management of acute diarrhea in adults. J Gastroenterol Hepatol 2002;17: S54-S71.(J.P. Cezard, E. Salazar-L)