NNITS-Nitazoxanide for Norovirus in Transplant Patients Study
Condition: Gastroenteritis Norovirus
MeSH terms: Gastroenteritis
Intervention: Nitazoxanide; Placebo
Intervention description: One 500 mg tablet twice daily with food for 56 consecutive doses; One tablet twice daily with food for 56 consecutive doses
Intervention MeSH terms: Nitazoxanide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 31.0
Sex: All
Minimum age: 12 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Efficacy; Hematopoietic Stem Cell; Nitazoxanide; Norovirus; Prospective, Randomized, Double-Blind Study; Safety; Solid Organ Transplant Recipients; Treatment

Summary:

      This is a phase 2 multi-center, double-blind, placebo-controlled study of the efficacy and
      safety of nitazoxanide for the treatment of solid organ and hematopoietic stem cell
      transplant recipients with symptomatic diarrhea due to Norovirus. The study involves a total
      of 160 Hematopoietic Stem Cell or Solid Organ transplant recipients, equal to or greater than
      12 years of age with diagnosis of Norovirus who will be selected and randomly assigned (1:1)
      to nitazoxanide or placebo group. The study duration is 60 months and subject participation
      duration is 6 months. Given the safety of prolonged therapy with nitazoxanide, lack of
      interactions with common post-transplant medications, putative antiviral activity and
      prolonged duration of viral shedding we are assessing 56 doses of therapy. The longitudinal
      monitoring phase will provide useful information on the course of host and viral responses in
      subjects with chronic Norovirus infection with and without treatment. Randomization will be
      stratified by age group (pediatric (12 through 17 years) vs. adult (greater than or equal to
      18 years)), chronicity of Norovirus-associated symptoms (acute (less than 14 days) vs.
      chronic (greater than or equal to 14 days)) and transplant type (solid organ (SOT)) vs.
      hematopoietic stem cell transplant (HSCT)). Enrolled subjects will participate in 2 phases of
      the study: Treatment Phase, which will include dosing with the assigned study agent for 28
      days. Longitudinal Monitoring Phase which will include telephone call on Days 35, 53, 113,
      173. Primary objective is 1) to assess the clinical efficacy of nitazoxanide for the
      management of acute and chronic Norovirus in transplant recipients.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects should meet all of the following inclusion criteria:

          1. Male or female age > / = 12 years.

          2. Recipient of a solid organ or hematopoietic stem cell transplant.

          3. Positive test result for Norovirus within 14 days of enrollment that is obtained as
             part of routine clinical care using a Norovirus testing available to the site.

          4. Active GI symptoms (diarrhea, or vomiting) that, in the opinion of the PI, are
             secondary to Norovirus. Patients must have active diarrhea, which is defined as at
             least 3 days of Bristol 6 or 7 stools in the past 2 weeks prior to enrollment per
             patient report.

          5. Willing and able to provide written informed consent and assent before initiation of
             any study procedures, consistent with local IRB policy.

          6. Subjects must be of non-childbearing potential or if of childbearing potential, must
             be using an effective method of birth control or must be abstinent.

               -  Non-childbearing potential is defined as surgically sterile or postmenopausal for
                  > one year.

               -  Effective methods of birth control include the use of hormonal or barrier birth
                  control such as implants, injectable contraceptives, combined oral
                  contraceptives, intrauterine devices (IUDs),or condoms with spermicidal agents
                  during study period. Female subjects must be using an effective method of birth
                  control or practice abstinence and must agree to continue such precautions during
                  the study and for 30 days after the Day 28 study visit.

               -  A woman is eligible if she is monogamous with a vasectomized male.This subject is
                  considered low risk and not required to use contraception.

          7. Agrees to complete all screening requirements, study visits and procedures.

        Exclusion Criteria:

        Subjects meeting any of the exclusion criteria at baseline will be excluded from study
        participation:

          1. Other identified infectious causes of diarrhea at screening. Alternative diagnosis
             requiring treatment would be considered a co-infection; if the testing is positive for
             a pathogen that the PI does not feel is causing the symptoms, they may be included but
             the PI or his/her designee must document that the positive test is not clinically
             significant, does not require treatment and is not causing the symptoms making the
             patient eligible for enrollment.

          2. Any condition that would, in opinion of the Site Investigator, place the subject at an
             unacceptable risk of injury or render the subject unable to meet the requirements of
             the protocol.

          3. Subjects receiving oral or intravenous immunoglobulin therapy concurrently or in the
             14 days prior to enrollment.

          4. Nitazoxanide use for any illness in the previous 30 days prior to randomization.

          5. Have received experimental products within 30 days prior to the study entry or plan to
             receive experimental products at any time during the study

          6. Known sensitivity to nitazoxanide or any of the excipients comprising the nitazoxanide
             tablets.

          7. Subjects unable to swallow oral medications.

          8. Subjects with ostomy.

          9. Women who are pregnant or lactating or have a positive urine pregnancy test at
             screening/enrollment/Day 1.