Safety, Efficacy and Cost-effectiveness of Racecadotril in Children With Acute Diarrhea in Mexico

NCT01153854 | Completed Phase 3 DMC

• 1 other identifier: INP14/2005-Raceca-001
• Study Type: interventional
• Target: 454
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• The pharmacoeconomics analysis

  2007-2009

Study Arms (4)

ORS-Raceca In hospital Group

EXPERIMENTAL

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

ORS-Placebo in hospital group

PLACEBO COMPARATOR

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

ORS-Placebo ambulatory group

PLACEBO COMPARATOR

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

ORS-Raceca ambulatory group

EXPERIMENTAL

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

Interventions

Racecadotril DRUG

oral racecadotril (1.5mg./Kg./t.i.d. doe 5 days) in double blind assigned.

ORS-Raceca In hospital Group; ORS-Raceca ambulatory group

Placebo groups DRUG

Placebo with feature color, appearance and tase similar to racecadotril t.i.d. for 5 days

ORS-Placebo ambulatory group; ORS-Placebo in hospital group

Eligibility Criteria

• Age: 1 Month - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Institute of Pediatrics, Mexico: lead
• Ferrer Laboratories: collaborator

Study Sites (1)

National Pediatric Institute

Mexico City, Mexico City, 04530, Mexico

Location

Related Publications (6)

• 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.

  PMID: 17767464 BACKGROUND

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

  PMID: 15923708 BACKGROUND

• 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.

  PMID: 12675192 BACKGROUND

• 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.

  PMID: 12205786 BACKGROUND

• 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.

  PMID: 11231932 BACKGROUND

• 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.

  PMID: 10944563 BACKGROUND

MeSH Terms

Conditions

Diarrhea

Interventions

racecadotril

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Pedro Gutierrez-Castrellon, MD, MSc, DSc

  National Pediatric Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: June 28, 2010
• First Posted: June 30, 2010
• Study Start: January 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: December 1, 2009
• Last Updated: June 30, 2010

Record last verified: 2010-06

Locations

ME (1)