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

Study Overview
=================
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.

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

Conditions
-----------------
Diarrhea

Intervention / Treatment
-----------------
* Drug: Racecadotril
* Drug: Placebo groups


Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 24 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ORS-Raceca In hospital Group<br>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<br>* oral racecadotril (1.5mg./Kg./t.i.d. doe 5 days) in double blind assigned.<br>|
| Placebo Comparator: ORS-Placebo in hospital group<br>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<br>* Placebo with feature color, appearance and tase similar to racecadotril t.i.d. for 5 days<br>|
| Placebo Comparator: ORS-Placebo ambulatory group<br>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<br>* Placebo with feature color, appearance and tase similar to racecadotril t.i.d. for 5 days<br>|
| Experimental: ORS-Raceca ambulatory group<br>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<br>* oral racecadotril (1.5mg./Kg./t.i.d. doe 5 days) in double blind assigned.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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)