Racecadotril for the treatment of severe acute watery diarrhoea in children admitted to the Kenyatta National hospital - a randomised double blinded placebo controlled trial
Date of Award
Master of Medicine (MMed)
Paediatrics and Child Health (East Africa)
Background: Diarrhoeal disease is the second most common cause of death in children under 5 years of age in Kenya. Treatment with Oral Rehydration Solution (ORS), elemental zinc and continued feeding (as recommended by the World Health Organisation) led to a significant reduction in mortality in the 1970s and 1980s, which has slowed since then. Adjunctive treatments have however, not gained much popularity either due to modest improvements in morbidity and mortality or unacceptable adverse effect profiles. Racecadotril, an enkephalinase inhibitor, has been used for over 2 decades in parts of Europe but is only recently gaining recognition in other parts of the world. No trials have been done testing its efficacy compared with the standard treatment recommended by the WHO (i.e. the combination of ORS and Zinc). This study aimed to measure the efficacy of racecadotril in the treatment of acute severe gastroenteritis disease in children admitted to hospital and on zinc.
Objectives: The primary objective was to compare the number of stools in the first 48 hours in children admitted with severe acute gastroenteritis treated with either Racecadotril or placebo. The secondary objectives were: to study the impact of Racecadotril on duration of inpatient stay as well as duration of illness in children admitted with severe acute gastroenteritis, and to describe the side effect profile of Racecadotril.
Methods: This was a parallel randomised double blinded placebo controlled trial. It enrolled children between the age of 3 and 60 months of age who were admitted to hospital with severe acute gastroenteritis as evidenced by a Vesikari score of greater than 11. Children who fulfilled the criteria for inclusion were enrolled after informed consent had been obtained from their parents/guardians. They were then randomised to receive either racecadotril or placebo in addition to the standard treatment prescribed by the admitting physicians. These children were followed up daily for: the number of stools for the first 48hrs, duration of admission, duration of illness and any adverse effects noted by the accompanying parents/guardians. The results were analysed by comparing the median number of stools using the Mann Whitney test.
Results: 156 children were screened, from which 120 were enrolled for the study and a final number of 58 in the placebo group and 57 in the drug group were analysed by intention to treat. There were no differences between the two groups when the numbers of stools at 48hours after introduction of the drug were compared: median (IQR) of 5 (3 - 7) and 5 (2.5 – 7.5) respectively, p value 0.63. On studying the duration of inpatient stay, this was also similar: drug group median (IQR): 4 days (1.5 - 6.5) and placebo group 4.5 (1.8 – 6.3), p value 0.71. The same was noted on comparing the duration of illness: 3 days (2 - 4) and 2 days (1 - 3), p value 0.77). Adverse events occurred in 14 subjects in both groups. The relative risk of a severe adverse event was 3.0 fold higher in the drug group but not statistically significant (95% CI 0.63 – 14.7) p value 0.16.
Conclusion: Based on the results of this study the impact of Racecadotril on the number of stools at 48 hours, duration of hospital stay and diarrhoea was not significant. Racecadotril, therefore, cannot be recommended as an adjunct for the treatment of severe acute gastroenteritis in children admitted to hospital and treated with ORS and Zinc.
Gharial, J. S. (2014). Racecadotril for the treatment of severe acute watery diarrhoea in children admitted to the Kenyatta National hospital - a randomised double blinded placebo controlled trial (Unpublished master's dissertation). Aga Khan University, East Africa.