Cholera
Conditions
Brief summary
Cholera still remains a global public health concern affecting both children and adults, and patients can succumb in quick time if remain untreated. Cholera is a secretory diarrhea and is generally treated with oral or intravenous rehydration therapy to compensate for the fluid loss. However, antimicrobial treatment is given to patients with moderate to severe diarrhea. The consistent emergence of multidrug-resistant bacteria is a major concern for the management of infectious diseases including cholera. No antisecretory drug has so far been proven successful. In a phase II clinical trial, the investigators will assess the effectiveness of a novel antisecretory drug VR-AD-1005 for treating cholera. Changes in stool volume and rehydration therapy will be assessed for VR-AD-1005 in comparison with placebo. If successful, this will be a huge advance in managing cholera and other secretory diarrhea. The introduction of the antisecretory drug can minimize the hospital stay and reduce antibiotic use, which in turn can reduce the emergence of antibiotic resistance among pathogens
Interventions
DRUGVR-AD-1005
oral capsule
DRUGPlacebo
oral capsule
Sponsors
Hunazine Biotech S.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
randomized, placebo-controlled, double-blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent. * Adults, both genders aged 18-65 years. * Acute watery diarrhea (defined as passage of three or more liquid stools within the 24 hours before admission) with severe dehydration on arrival. * Detection of V. cholerae by rapid diagnostic assay (e.g. dark field microscopy).
Exclusion criteria
* Known or suspected hypersensitivity to trial product(s) or related products. * Subjects with passage of bloody stools or muco-purulent stools. * Subjects with chronic diarrhea (\>4 weeks of Diarrhea). * Clinically significant concomitant systemic disease (i.e. cardiovascular diseases including heart failure, acute kidney injury, sepsis or life-threatening malignant cancer). * Mental incapacity, unwillingness, or language barriers, precluding adequate understanding or cooperation. * History of receiving antimicrobial or antidiarrheal drugs within 6 hours prior to admission. * Positive urine pregnancy test for all female patients * Failure to obtain informed consent. * Failure to definitively diagnose cholera via culture or RT-PCR
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stool Output Volume During Treatment Period. | Stool output volume was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours, e.g. hour 1, hour 6, hour 8, hour 10, hour 11, hour 22, hour 23, hour 26, etc.). | Means of stool output data expressed as ml/kg·h-1 for Treatment and Comparator groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Stool Output in Excess of 200 ml/Hour | Stool output volume was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours). | For analysis, individual stool charts were used to calculate stool output per patient per hour and express it as stool volume in ml/hour. Duration of time during treatment when stool output was in excess of 200ml/hour was calculated for each participant and compared for control and study intervention groups. |
| Number of Unscheduled IV Rehydration Episodes Per Treatment | Unscheduled IV rehydration episodes were measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours). | Average number of unscheduled IV rehydration episodes per participant per study arm. |
| Volume of IV Rehydration, ml/kg | Volume of administered IV rehydration solution was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours). | Average volume of IV rehydration per subject per treatment arm was calculated as aggregate per time period. Data were analyzed for three time periods, namely 0-12 hours; 0-24 hours; and the entire duration of treatment. For each period, mean volume of the infusion was calculated and expressed in ml/kg body weight. |
| Time Until Last Liquid Stool | Liquid and solid stool output was measured by trained trial personnel and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours). | Diarrhea duration is measured from the first dose of study drug to resolution. Time (hours) from start of treatment until the last liquid stool was determined for each participant. Data were extracted from individual stool charts, and time-to-criterion was analyzed using log-rank statistics between the Treatment and the Comparator groups. |
| Duration of Stool Output in Excess of 400 mL/Hour | Stool output volume was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours). | For analysis, individual stool charts were used to calculate stool output per patient per hour and express it as stool volume in ml/hour. Duration of time during treatment when stool output was in excess of 400ml/hour was calculated for each participant and compared for control and study intervention groups. |
| Participants With at Least One Adverse Event | From enrollment until the end of follow-up, up to 28 days | Proportion of participants experiencing at least one adverse event (including serious adverse events) following administration of study treatment during the safety evaluation period. |
Countries
Bangladesh
Participant flow
Recruitment details
This study recruited 150 participants in total, meeting the inclusion criteria, of which 75 participants were double-blindly assigned to the Active Arm and 75 participants were assigned to the Placebo Arm.
Pre-assignment details
Participants were randomized in a 1:1 ratio. VR-AD-1005 oral capsule was administered orally 4 times per day (approximately every 4-5 hours with overnight break to allow for participants rest and recovery) with first administration of 3 capsules as loading dose
Baseline characteristics
| Characteristic | — |
|---|---|
| Acute watery diarrhea | 15.57 hours STANDARD_DEVIATION 11.12 |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 142 Participants |
| Episodes (diarrhea) | 26.03 number of episodes STANDARD_DEVIATION 14.55 |
| Episodes (vomiting) | 10.37 number of episodes STANDARD_DEVIATION 7.3 |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 55 Participants |
| Vomiting | 10.36 hours STANDARD_DEVIATION 8.64 |
| Weight | 52.97 kg STANDARD_DEVIATION 9.99 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 75 | 0 / 75 |
| other Total, other adverse events | 0 / 75 | 0 / 75 |
| serious Total, serious adverse events | 1 / 75 | 0 / 75 |
Outcome results
None listed