PROCLAIM -- Misoprostol in the Prevention of Recurrent CDI Prevent Recurrence of Clostridium Difficile Infection With Misoprostol (PROCLAIM)

A Randomized, Double-Blind, Placebo-Controlled Trial to Assess The Efficacy and Safety of Misoprostol in The Prevention of Recurrence of Clostridium Difficile Infection in Adults

A total of 440 patients meeting enrollment criteria with a primary episode of C. Difficile Infection (CDI) will be enrolled across 3 sites. The total study time period for study procedures followed by clinical monitoring is anticipated to be about 24 months (biomarker assays and other analyses may be completed after the 24 month time period). All participants will receive oral antibiotics for CDI under the care of their physician. After consenting to participate in the study, participants will be randomized to receive either misoprostol (200 mcg po BID) or matching placebo for 14 days. Participants will be monitored for a total time-period of approximately 9 weeks with the goal of monitoring for recurrence of CDI during an 8-week follow-up period from the time that the course of antibiotic treatment is completed. Patients will have blood and stool samples (or rectal swabs if participants are unable to provide a stool sample) collected throughout the study to assess adherence, biomarkers, and to confirm recurrence of CDI (if necessary).

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile
• Intervention / Treatment: Drug: Misoprostol 100Mcg Tab; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Episode of CDI, defined as ALL of the following:

   1. ≥3 unformed (loose or watery) stools with a 24-hour period;
   2. A documented positive C. difficile toxin assay (enzyme immunoassay [EIA] or cell cytotoxicity assay) or NAAT for toxigenic C. difficile from a stool sample collected while the subject was symptomatic; and
   3. No other explanation for diarrhea (e.g. laxatives).
2. At the time of enrollment, on a course of oral antibiotics commonly used for treatment of CDI.
3. Be ≥18 years of age.
4. Be able to provide signed and dated informed consent.
5. Must be able to read and understand English.

Exclusion Criteria

1. Have not recovered from primary episode of CDI at time of enrollment, defined as presence of EITHER of the following:

   1. ≥3 unformed (loose or watery) stools during the 24 hours prior to randomization, OR
   2. Abdominal discomfort (more than mild) present during the 24 hours prior to randomization.

2. Have received, or plans to use, any of the following for treatment of the primary episode of CDI:

   1. Any immunotherapy (e.g., intravenous immunoglobulin, bezlotoxumab).
   2. Any toxin-binding therapy (e.g., cholestyramine [Questran], colestipol [Colestid], or colesevelam [Welchol]).
3. Current or planned treatment with prostanoid therapy.
4. Diarrhea caused by another infection or diarrhea caused by an underlying gastrointestinal disorder.
5. Have any contraindication to oral/enteral therapy (e.g., severe nausa/vomiting or ileus).
6. Have an absolute neutrophil count <500/mm3 [1.0 x 109/L] within 30 days of screening.
7. Require or have an anticipated need for mechanical ventilation or vasopressors for hemodynamic support during the study.
8. Pregnant, nursing, or planning to become pregnant.
9. Inability to understand the requirements of the study, inability to abide by the study restrictions.
10. Have any clinically significant medical or surgical condition that in the investigator's opinion could interfere with the administration of study drug, interpretation of study results, or compromise the safety or well-being of the subject.
11. Known hypersensitivity to misoprostol.
12. Be unwilling or unable to follow study procedures (e.g., study visits, swallow the study drug/placebo, provide stool samples and undergo phlebotomy according to the study schedule, and reliably report information by phone), or not have a caregiver who can ensure that study procedures are followed.
13. If female, be pre-menopausal (cessation of menses less than or equal to 1 year) and not surgically/medically sterile or not following acceptable non-hormonal method of birth control such as abstinence, intrauterine device, or barrier control for at least 1 complete menstrual cycle before the screening visit, or not using estrogen/progestin containing products for at least 2 months before the screening visit through discharge from the study.
14. Unreliable access to telephone service to allow for contact with study personnel.
15. Inability to be seen for routine clinical care either as an outpatient or inpatient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Two capsules twice per day
Experimental: Study Drug (Misoprostol)	Drug: Misoprostol 100Mcg Tab; Two 100mcg capsules twice per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinical Recurrence of Clostridium Difficile Infection (CDI).	Number of Participants with clinical recurrence of Clostridium Difficile Infection (CDI) in the 8 week follow-up period.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Recurrences During the Follow-up Period	Number of recurrences during the follow-up period (for those who have a first recurrence during the follow-up time period)	8 weeks
Time to Resolution of Diarrhea	Time to resolution of diarrhea (TTROD; for those with recurrence)	8 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2018
• Primary Completion (Actual): September 22, 2021
• Study Completion (Actual): September 22, 2021

Study Registration Dates

• First Submitted: August 1, 2018
• First Submitted That Met QC Criteria: August 1, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Recurrence; Clostridium Infections; Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: 172163; U01TR002398 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No