Assessment of a Novel Fixed-dose Combination (FDC) Drug VR-AD-1005 for the Treatment of Acute Watery Diarrhea in Cholera

Phase 2CompletedNCT06193408

Hunazine Biotech S.L.150 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

150

Conditions

Cholera

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Stool Output Volume During Treatment Period.

Means of stool output data expressed as ml/kg·h-1 for Treatment and Comparator groups.

Time frame: 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.).

Secondary Outcomes

Duration of Stool Output in Excess of 200 ml/Hour

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.

Time frame: Stool output volume was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours).

Number of Unscheduled IV Rehydration Episodes Per Treatment

Average number of unscheduled IV rehydration episodes per participant per study arm.

Time frame: Unscheduled IV rehydration episodes were measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours).

Volume of IV Rehydration, ml/kg

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 frame: 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).

Time Until Last Liquid Stool

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.

Time frame: 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).

Duration of Stool Output in Excess of 400 mL/Hour

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.

Time frame: Stool output volume was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours).

Participants With at Least One Adverse Event

Proportion of participants experiencing at least one adverse event (including serious adverse events) following administration of study treatment during the safety evaluation period.

Time frame: From enrollment until the end of follow-up, up to 28 days