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NNITS-Nitazoxanide for Norovirus in Transplant Patients Study

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ClinicalTrials.gov Identifier: NCT03395405
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : October 23, 2020
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Condition or disease Intervention/treatment Phase
Gastroenteritis Norovirus Drug: Nitazoxanide Other: Placebo Phase 2

Detailed Description:
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) into two treatment groups: nitazoxanide or placebo. The study duration is approximately 60 months and subject participation duration is approximately 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. Secondary Objectives are 1) to assess the virologic efficacy of nitazoxanide and 2) to assess the safety of nitazoxanide for the management of acute and chronic Norovirus in transplant recipients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Multi-Center, Prospective, Randomized, Double-Blind Study to Assess the Clinical and Antiviral Efficacy and Safety of Nitazoxanide for the Treatment of Norovirus in Hematopoietic Stem Cell and Solid Organ Transplant Recipients
Actual Study Start Date : October 15, 2018
Estimated Primary Completion Date : May 22, 2021
Estimated Study Completion Date : May 22, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nitazoxanide Arm
500 mg (one tablet) nitazoxanide by mouth twice daily with food for 56 consecutive doses. N=80
Drug: Nitazoxanide
One 500 mg tablet twice daily with food for 56 consecutive doses

Placebo Comparator: Placebo Arm
Placebo (one tablet) by mouth twice daily with food for 56 consecutive doses. N=80
Other: Placebo
One tablet twice daily with food for 56 consecutive doses




Primary Outcome Measures :
  1. The time from randomization until cessation of vomiting for at least 48 hours, assessed from the daily diary [ Time Frame: Day 1 through day 180 ]
  2. The time from randomization until no diarrhea (type 6 or 7 by Bristol Stool Chart) assessed from the daily diary [ Time Frame: Day 1 through day 180 ]

Secondary Outcome Measures :
  1. The change in viral titer [ Time Frame: Day 1 through day 180 ]
  2. The incidence of abnormal Alanine Aminotransferase (ALT) level [ Time Frame: Day 1 through day 60 ]
  3. The incidence of abnormal Alkaline Phosphatase level [ Time Frame: Day 1 through day 60 ]
  4. The incidence of abnormal Aspartate Aminotransferase (AST) level [ Time Frame: Day 1 through day 60 ]
  5. The incidence of abnormal Bilirubin level [ Time Frame: Day 1 through day 60 ]
  6. The incidence of abnormal Blood Urea Nitrogen (BUN) level [ Time Frame: Day 1 through day 60 ]
  7. The incidence of abnormal Creatinine level [ Time Frame: Day 1 through day 60 ]
  8. The incidence of abnormal Hemoglobin level [ Time Frame: Day 1 through day 60 ]
  9. The incidence of abnormal Platelet count [ Time Frame: Day 1 through day 60 ]
  10. The incidence of abnormal White Blood Cell (WBC) count [ Time Frame: Day 1 through day 60 ]
  11. The incidence of Hospitalization [ Time Frame: Day 1 through day 60 ]
  12. The incidence of protocol-specified serious adverse events [ Time Frame: Day 1 through day 60 ]
  13. The incidence of unsolicited non-serious adverse events [ Time Frame: Day 1 through day 60 ]
  14. The Time from randomization to first negative viral load [ Time Frame: Day 1 through day 180 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 99 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03395405


Contacts
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Contact: Michael Grundel Ison 13126954186 mgison@northwestern.edu

Locations
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United States, Alabama
University of Alabama Hospital - Infectious Diseases Withdrawn
Birmingham, Alabama, United States, 35249-0001
United States, Illinois
Northwestern University - Comprehensive Transplant Center Recruiting
Chicago, Illinois, United States, 60611-2927
United States, Kansas
University of Kansas Medical Center - Infectious Diseases Recruiting
Kansas City, Kansas, United States, 66160-8500
United States, Maryland
Johns Hopkins Hospital - Medicine - Infectious Diseases Recruiting
Baltimore, Maryland, United States, 21287-0005
United States, Michigan
University of Michigan School of Public Health - Epidemiology Not yet recruiting
Ann Arbor, Michigan, United States, 48109-2029
University of Michigan - Infectious Disease Clinic at Taubman Center Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Nebraska
University of Nebraska Medical Center - Infectious Diseases Recruiting
Omaha, Nebraska, United States, 68198-5400
United States, Ohio
Cincinnati Children's Hospital Medical Center - Infectious Diseases Not yet recruiting
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
University of Pittsburgh - Medicine - Infectious Diseases Recruiting
Pittsburgh, Pennsylvania, United States, 15213-3403
Children's Hospital of Pittsburgh of UPMC - Pediatric Infectious Diseases Recruiting
Pittsburgh, Pennsylvania, United States, 15224-1529
United States, Texas
University of Texas Southwestern Medical Center - Internal Medicine Subspecialties Clinic Recruiting
Dallas, Texas, United States, 75390-8884
United States, Washington
Fred Hutchinson Cancer Research Center - Vaccine and Infectious Diseases Recruiting
Seattle, Washington, United States, 98109-4433
University of Washington - Medicine Recruiting
Seattle, Washington, United States, 98195-7110
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03395405    
Other Study ID Numbers: 16-0092
HHSN272201600016C
First Posted: January 10, 2018    Key Record Dates
Last Update Posted: October 23, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Efficacy
Hematopoietic Stem Cell
Nitazoxanide
Norovirus
Prospective, Randomized, Double-Blind Study
Safety
Solid Organ Transplant Recipients
Treatment
Additional relevant MeSH terms:
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Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Nitazoxanide
Antiparasitic Agents
Anti-Infective Agents