Safety, Efficacy and Cost-effectiveness of Racecadotril in Children With Acute Diarrhea in Mexico (Raceca-Mex)

Efficacy, Safety and Cost-effectiveness Analysis of Impact of Racecadotril as an Adjunct in the Treatment of Acute Diarrhea in Mexican Children

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.

Study Overview

• Status: Completed
• Conditions: Diarrhea
• Intervention / Treatment: Drug: Racecadotril; Drug: Placebo groups

• Study Type: Interventional
• Enrollment (Actual): 454
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico city, Mexico, 04530
    • National Pediatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ORS-Raceca In hospital Group; This group included 135 dehydrated patients which need an oral rehydration therapy in hospital and were assigned to received oral rehydration solution and racecadotril (1.5mg./Kg./t.i.d. doe 5 days) in double blind assigned.	Drug: Racecadotril; oral racecadotril (1.5mg./Kg./t.i.d. doe 5 days) in double blind assigned.
Placebo Comparator: ORS-Placebo in hospital group; This group included 135 dehydrated patients which need an oral rehydration therapy in hospital and were assigned to received oral rehydration solution and placebo in double blind assigned.	Drug: Placebo groups; Placebo with feature color, appearance and tase similar to racecadotril t.i.d. for 5 days
Placebo Comparator: ORS-Placebo ambulatory group; This group included 92 non dehydrated patients which were assigned to received oral rehydration solution and placebo in double blind assigned and ambulatory (in home) bases.	Drug: Placebo groups; Placebo with feature color, appearance and tase similar to racecadotril t.i.d. for 5 days
Experimental: ORS-Raceca ambulatory group; This group included 92 non dehydrated patients which were assigned to received oral rehydration solution and racecadotril (1.5mg./Kg./t.i.d. doe 5 days) in double blind assigned and ambulatory (in home) bases.	Drug: Racecadotril; oral racecadotril (1.5mg./Kg./t.i.d. doe 5 days) in double blind assigned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool output rate	During the study, since the inclusion until the end of the diarrheic episode (24hs after passage of liquid or semiliquid stool) we will measure the stool output rate, reporting it at 48h and at seven day.	2007-2009
Duration of diarrhea	In all included patients we will measure the duration of diarrhea, marking as a zero time the moment to sign the informed consent and the end of the diarrheic episod 24hs after the passage of the last liquid or semiliquid stool	2007-2009
Percentage of related adverse events	During the duration of the study and five days after we will measure the presence of related adverse events. Any possible event ocurred after sign of consented inform will record and then classified as related or non related and as severe or notr severe adverse event	2007-2009

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pharmacoeconomics analysis	The pharmacoeconomics model consisted in a theoretical scheme that makes it possible to conduct simulations of health processes associated with medical care, use of medications, expenses for intravenous hydration and re-hospitalizations secondary to dehydration, through estimates obtained from the efficacy data available from our clinical trial as well as the costs and consequences. The model was prepared using the TreeAge Pro Healthcare v 1.2.0, 2009 software tool	2007-2009

Collaborators and Investigators

• Sponsor: National Institute of Pediatrics, Mexico
• Collaborators: Ferrer Laboratories
• Investigators: Principal Investigator: Pedro Gutierrez-Castrellon, MD, MSc, DSc, National Pediatric Institute

Publications and helpful links

General Publications

• 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.
• Cezard JP, Salazar-Lindo E. Racecadotril in acute diarrhea. Indian Pediatr. 2005 May;42(5):502-3; author reply 503. No abstract available.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: June 28, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (Estimate): June 30, 2010

Study Record Updates

• Last Update Posted (Estimate): June 30, 2010
• Last Update Submitted That Met QC Criteria: June 29, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• 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)
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Protease Inhibitors; Antidiarrheals; Racecadotril
• Other Study ID Numbers: INP14/2005-Raceca-001