Diarrhea
Conditions
Brief summary
Multicenter, open-label, controlled, randomized clinical study to evaluate the efficacy and safety of Racecadotril in infants, children and adolescents with acute diarrhea
Interventions
Racecadotril plus ORS
DRUGORS
ORS
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent from one of the parent(s)/caregiver(s) or subject informed assent * Children and adolescents, both genders, age from 3 months to \< 18 years of age * Confirmed diagnosis of acute diarrhea (defined as the passage of three or more unformed or liquid stools within the last 24 hours and lasting for less than three days) * Females of child-bearing potential should agree to continue using a medically acceptable method of birth control throughout the study and for 30 days immediately after the last dose of study drug. Medically acceptable methods of birth control include bilateral tubal ligation or the use of either a contraceptive implant, a contraceptive injection, an intrauterine device, or an oral contraceptive taken within the past three months where the subject agrees to continue using during the study or to adopt another birth control method, or a double-barrier method which consists of a combination of any two of the following: diaphragm, cervical cap, condom, or spermicide
Exclusion criteria
* Known allergy to Racecadotril or any of its ingredients * Subjects suffering from renal or hepatic impairment * Subjects who need treatment for diarrhea other than ORS alone * Subjects with fever \> 39 degrees Celsius * Subjects with bloody and/or purulent stools * Subjects suffering from antibiotic-associated diarrhea, chronic diarrhea or iatrogenic diarrhea * Subjects with alternating bouts of diarrhea and constipation * Diarrhea due to exacerbation of chronic gastrointestinal diseases such as irritable bowel syndrome, inflammatory bowel disease or pancreatic exocrine insufficiency * Cystic fibrosis or coeliac disease * Subjects suffering from prolonged or uncontrolled vomiting * Subjects with rare hereditary problems of fructose or galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption syndrome or sucrase isomaltase insufficiency or primary or secondary lactase insufficiency * Subjects having received antibiotic treatment at any time within 30 days prior to inclusion into the study * Subjects having received antidiarrheal drugs 48 hours prior to inclusion into the study * Subjects with severe dehydration required for intravenous/parenteral rehydration * Subjects who have reported angioedema with angiotensin converting enzyme inhibitors (such as captopril, enalapril, lisinopril, perindopril, ramipril) * Subjects with combined diseases or medical situations that would prevent to be enrolled depending in the judgment of the investigator * Intake of experimental drug within 30 days prior to study start * Subjects with contraindications to ORS or for whom warnings/precautions of ORS apply * Adolescents (≥ 60 kg) not able to swallow capsules * Pregnancy and lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Diarrhea (Hours) Between the Start of Treatment Until Last Diarrheal/Watery Stool Before Recovery or End of Study Treatment (Treatment Duration Maximal 5 Days) | 5 days | Duration of diarrhea is defined by date and time of the evacuation of the final diarrheal stool derived from the daily diary. Log-rank test was performed with a p-value \< 0.0001 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Recovered Subjects Per Treatment Group. | 5 days | Number of recovered subjects per treatment group. Recovery is defined as the evacuation of the first of two consecutive normal stools or no stool within 12 h within treatment period |
| Number of Recovered Subjects as Defined by Global Physician Assessment of Success at the End of Treatment | 5 days | Globabl physician assessment used 6 scores with a score of 1 or 2 being regarded as treatment success |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Racecadotril Plus Standard Treatment Oral Rehydration Solution Racecadotril plus ORS: Racecadotril plus ORS | 62 |
| ORS (Standard Treatment) ORS: ORS | 62 |
| Total | 124 |
Baseline characteristics
| Characteristic | ORS (Standard Treatment) | Total | Racecadotril Plus Standard Treatment Oral Rehydration Solution |
|---|---|---|---|
| Age, Categorical <=18 years | 62 Participants | 124 Participants | 62 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 6.8 years STANDARD_DEVIATION 4.6 | 6.5 years STANDARD_DEVIATION 4.5 | 6.2 years STANDARD_DEVIATION 4.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 59 Participants | 120 Participants | 61 Participants |
| Region of Enrollment Russia | 62 Participants | 124 Participants | 62 Participants |
| Sex: Female, Male Female | 33 Participants | 57 Participants | 24 Participants |
| Sex: Female, Male Male | 29 Participants | 67 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 62 |
| other Total, other adverse events | 0 / 62 | 0 / 62 |
| serious Total, serious adverse events | 0 / 62 | 0 / 62 |
Outcome results
Primary
Duration of Diarrhea (Hours) Between the Start of Treatment Until Last Diarrheal/Watery Stool Before Recovery or End of Study Treatment (Treatment Duration Maximal 5 Days)
Duration of diarrhea is defined by date and time of the evacuation of the final diarrheal stool derived from the daily diary. Log-rank test was performed with a p-value \< 0.0001
Time frame: 5 days
Population: full analysis sample
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Racecadotril Plus Standard Treatment Oral Rehydration Solution | Duration of Diarrhea (Hours) Between the Start of Treatment Until Last Diarrheal/Watery Stool Before Recovery or End of Study Treatment (Treatment Duration Maximal 5 Days) | 20.0 hours | Standard Deviation 2.2 |
| ORS (Standard Treatment) | Duration of Diarrhea (Hours) Between the Start of Treatment Until Last Diarrheal/Watery Stool Before Recovery or End of Study Treatment (Treatment Duration Maximal 5 Days) | 43.2 hours | Standard Deviation 3.4 |
Secondary
Number of Recovered Subjects as Defined by Global Physician Assessment of Success at the End of Treatment
Globabl physician assessment used 6 scores with a score of 1 or 2 being regarded as treatment success
Time frame: 5 days
Population: full analysis sample
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Racecadotril Plus Standard Treatment Oral Rehydration Solution | Number of Recovered Subjects as Defined by Global Physician Assessment of Success at the End of Treatment | 62 Participants |
| ORS (Standard Treatment) | Number of Recovered Subjects as Defined by Global Physician Assessment of Success at the End of Treatment | 60 Participants |
Secondary
Number of Recovered Subjects Per Treatment Group.
Number of recovered subjects per treatment group. Recovery is defined as the evacuation of the first of two consecutive normal stools or no stool within 12 h within treatment period
Time frame: 5 days
Population: full analysis sample
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Racecadotril Plus Standard Treatment Oral Rehydration Solution | Number of Recovered Subjects Per Treatment Group. | 62 Participants |
| ORS (Standard Treatment) | Number of Recovered Subjects Per Treatment Group. | 58 Participants |