PROCLAIM -- Misoprostol in the Prevention of Recurrent CDI Prevent Recurrence of Clostridium Difficile Infection With Misoprostol
Condition: Clostridium Difficile
MeSH terms: Clostridium Infections; Recurrence
Intervention: Misoprostol 100Mcg Tab; Placebo
Intervention description: Two 100mcg capsules twice per day; Two capsules twice per day
Intervention MeSH terms: Misoprostol
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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.