Clinical trial NCT01153854: Safety, Efficacy and Cost-effectiveness of Racecadotril in Children With Acute Diarrhea in Mexico
Official title: Efficacy, Safety and Cost-effectiveness Analysis of Impact of Racecadotril as an Adjunct in the Treatment of Acute Diarrhea in Mexican Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diarrhea
Keywords: acute diarrhea
Acute diarrhea (three or more watery or semi-watery bowel movements for at least one day lasting no more than 5 days before being admitted)
Lead sponsor: National Institute of Pediatrics, Mexico
Sponsor class: OTHER_GOV
Collaborators: name: Ferrer Laboratories
First posted: 2010-06-30
Enrollment: 454
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rationale: Acute diarrhea (AD) is still a significant morbidity-mortality problem worldwide. Although oral rehydration therapy is the cornerstone, its anti-diarrheal effect is a controversial subject. Since ten years ago, Racecadotrilo´s safety and efficacy had been proved. However, a pharmacoeconomics analysis on this therapeutics has not been published yet.

Objective: Evaluate the efficacy, safety, tolerability and costs associated with Racecadotril administration in comparison to a placebo in infants up to 24 months of age with AD in a hospital (mildly or moderately dehydrated) and ambulatory (no dehydrated) settings at the National Institute of Pediatrics in Mexico.

Material and Methods: Randomized, double-blind, placebo controlled, clinical trial (RDBCCT) with pharmacoeconomics analysis (cost minimization) to realize in 454 infants with AD (270 hospitalized and 184 outpatients), 1 to 24 months of age who concomitantly will receive ORT and Racecadotril (1.5mg./Kg./t.i.d. doe 5 days) (ORT-Rac Group) or placebo (ORT-Placebo Group). The clinical outcomes in the hospitalized infants to measure will be a) Stool output rate at 48hs. and at the end of the study; b) duration of diarrhea; c) percentage of intravenous (IV) needs and d) percentage of adverse events. The outcome variables in outpatient infants to measure will be a) total liquid and semi-liquid bowel movements during the study; b) duration of diarrhea and c) percentage of adverse events. The pharmacoeconomics analysis will involve a cost minimization analysis (CMA). Results will be analyzed through bi and multivariate analysis using STATA 11.0 for Mac, considering a p value \< 0.05 as significant. The pharmacoeconomics model will made through decisions trees using TreAge Pro Healthcare v 1.2.0, 2009.


Eligibility criteria: Inclusion Criteria:

* children ≥ 1 month of age and ≤ 24 months of age
* Acute diarrhea (defined as three or more watery or semi-watery bowel movements for at least one day lasting no more than 5 days before being admitted)
* For in hospital group: mild or moderate dehydration
* Signed informed consent letter

Exclusion Criteria:

* previous use of oral antibiotics for more than 48 hours (during the two weeks before the trial
* previous use of anti-diarrheal medication (e.g.: bismuth subsalicylate, adsorbents, Loperamide, combinations)
* chronic pathologies (e.g.: cardiopathies, nephropathies, chronic gastrointestinal pathologies, endocrinopathies)

Primary outcomes:
measure: Stool output rate
timeFrame: 2007-2009
measure: Duration of diarrhea
timeFrame: 2007-2009
measure: Percentage of related adverse events
timeFrame: 2007-2009
Secondary outcomes:
measure: The pharmacoeconomics analysis
timeFrame: 2007-2009
Other outcomes:
Locations:
city: Mexico city
country: Mexico
facility: National Pediatric Institute
Study officials:
affiliation: National Pediatric Institute
name: Pedro Gutierrez-Castrellon, MD, MSc, DSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Szajewska H, Ruszczynski M, Chmielewska A, Wieczorek J. Systematic review: racecadotril in the treatment of acute diarrhoea in children. Aliment Pharmacol Ther. 2007 Sep 15;26(6):807-13. doi: 10.1111/j.1365-2036.2007.03444.x.
citation: Cezard JP, Salazar-Lindo E. Racecadotril in acute diarrhea. Indian Pediatr. 2005 May;42(5):502-3; author reply 503. No abstract available.
citation: Rao SG. Racecadotril (acetorphan) in the treatment of acute watery diarrhoea in children. J Indian Med Assoc. 2002 Aug;100(8):530. No abstract available.
citation: Cojocaru B, Bocquet N, Timsit S, Wille C, Boursiquot C, Marcombes F, Garel D, Sannier N, Cheron G. [Effect of racecadotril in the management of acute diarrhea in infants and children]. Arch Pediatr. 2002 Aug;9(8):774-9. doi: 10.1016/s0929-693x(01)00988-5. French.
citation: Cezard JP, Duhamel JF, Meyer M, Pharaon I, Bellaiche M, Maurage C, Ginies JL, Vaillant JM, Girardet JP, Lamireau T, Poujol A, Morali A, Sarles J, Olives JP, Whately-Smith C, Audrain S, Lecomte JM. Efficacy and tolerability of racecadotril in acute diarrhea in children. Gastroenterology. 2001 Mar;120(4):799-805. doi: 10.1053/gast.2001.22544.
citation: Salazar-Lindo E, Santisteban-Ponce J, Chea-Woo E, Gutierrez M. Racecadotril in the treatment of acute watery diarrhea in children. N Engl J Med. 2000 Aug 17;343(7):463-7. doi: 10.1056/NEJM200008173430703.