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Gastroenteritis NorovirusPhase 2NCT03395405

NNITS-Nitazoxanide for Norovirus in Transplant Patients Study

A Phase 2 study testing Nitazoxanide in people with Gastroenteritis Norovirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 to 99 years
Conditions the study is for
Gastroenteritis Norovirus
What is being tested?
Nitazoxanide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
31 participants
Where
12 sitesUnited States
Study dates
15 Oct 2018to 24 Aug 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 99 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Subjects should meet all of the following inclusion criteria:
  • Male or female age > / = 12 years.
  • Recipient of a solid organ or hematopoietic stem cell transplant.
  • 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.
  • 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.
  • Willing and able to provide written informed consent and assent before initiation of any study procedures, consistent with local IRB policy.
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  • 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.
  • Agrees to complete all screening requirements, study visits and procedures.

Who cannot join

  • Subjects meeting any of the exclusion criteria at baseline will be excluded from study participation:
  • 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.
  • 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.
  • Subjects receiving oral or intravenous immunoglobulin therapy concurrently or in the 14 days prior to enrollment.
  • Nitazoxanide use for any illness in the previous 30 days prior to randomization.
  • Have received experimental products within 30 days prior to the study entry or plan to receive experimental products at any time during the study
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  • Known sensitivity to nitazoxanide or any of the excipients comprising the nitazoxanide tablets.
  • Subjects unable to swallow oral medications.
  • Subjects with ostomy.
  • Women who are pregnant or lactating or have a positive urine pregnancy test at screening/enrollment/Day 1.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites
  • University of Michigan School of Public Health - Epidemiology

    Ann Arbor, Michigan, 48109-2029

  • University of Michigan - Infectious Disease Clinic at Taubman Center

    Ann Arbor, Michigan, 48109

  • Johns Hopkins Hospital - Medicine - Infectious Diseases

    Baltimore, Maryland, 21287-0005

  • Northwestern University - Comprehensive Transplant Center

    Chicago, Illinois, 60611-2927

  • Cincinnati Children's Hospital Medical Center Vaccine Research Center

    Cincinnati, Ohio, 45229-3039

  • University of Texas Southwestern Medical Center - Internal Medicine Subspecialties Clinic

    Dallas, Texas, 75390-8884

  • University of Kansas Medical Center - Infectious Diseases

    Kansas City, Kansas, 66160-8500

  • University of Nebraska Medical Center - Infectious Diseases

    Omaha, Nebraska, 68198-5400

  • University of Pittsburgh - Medicine - Infectious Diseases

    Pittsburgh, Pennsylvania, 15213-3403

  • Children's Hospital of Pittsburgh of UPMC - Pediatric Infectious Diseases

    Pittsburgh, Pennsylvania, 15224-1529

  • Fred Hutchinson Cancer Research Center - Vaccine and Infectious Diseases

    Seattle, Washington, 98109-4433

  • University of Washington - Medicine

    Seattle, Washington, 98195-7110

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Nitazoxanide, Placebo
Keywords
Efficacy, Hematopoietic Stem Cell, Nitazoxanide, Norovirus, Prospective, Randomized, Double-Blind Study, Safety, Solid Organ Transplant Recipients, Treatment

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NitazoxanideDrug

    One 500 mg tablet twice daily with food for 56 consecutive doses

  • PlaceboOther

    One tablet twice daily with food for 56 consecutive doses

Study groups in NCT03395405
Study groupRoleWhat they receive
Nitazoxanide ArmExperimental500 mg (one tablet) nitazoxanide by mouth twice daily with food for 56 consecutive doses. N=80
Receives: Drug: Nitazoxanide
Placebo ArmPlacebo comparatorPlacebo (one tablet) by mouth twice daily with food for 56 consecutive doses. N=80
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to Initial Clinical Resolution of Norovirus Symptoms

    Time (in days) from randomization until the study day when clinical resolution occurred. Clinical resolution was assessed from participant's daily diaries and was defined as cessation of vomiting and no stools classified by the Bristol Stool Chart as diarrhea (Type 6 or 7) for at least 48 hours.

    Measured: 48 hours through Day 180

Secondary outcomes (6)
  1. Number of Participants Experiencing Laboratory Adverse Events (AEs)

    Participants experiencing at least one new laboratory adverse event. Laboratory parameters include White Blood Cell (WBC), Hemoglobin, Platelet Count, Creatinine, Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Blood Urea Nitrogen (BUN), and Bilirubin. Laboratory results were considered AEs using the following thresholds : WBC greater than the upper limit of normal (ULN), hemoglobin less than the lower limit of normal (LLN), platelet count less than the LLN; creatinine greater than the ULN; alkaline phosphatase greater than the ULN; ALT greater than the ULN, AST greater than the ULN, BUN greater than or equal to the ULN, and bilirubin greater than the ULN. ULN and LLN values differed by site, sex, and age category.

    Measured: Day 1 (baseline) through Day 60

  2. Change in Viral Titer (Day 1 to Day 180)

    Change in viral titer defined as the difference between the Day 180 viral titer and the Day 1 viral titer. Participants were analyzed for the viral load test type (Norovirus GII or Norovirus GI) that they tested positive for at baseline (Day 1).

    Measured: Day 1 (baseline) and Day 180

  3. Number of Participants Reporting Hospitalization

    Hospitalizations included any admission to a hospital for treatment and were not reported as Serious Adverse Events (SAEs).

    Measured: Day 1 (baseline) through Day 60

  4. Number of Participants Reporting Protocol-Specified SAEs

    Protocol-specified SAEs included any adverse event or suspected adverse reaction which, in the view of the investigator or sponsor, resulted in any of the following: death, life threatening adverse event, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life function, congenital anomaly or birth defect, or an important medical event that may jeopardize the participant and require medical or surgical intervention. Hospitalizations were collected as a secondary outcome measure and were not reported as SAEs.

    Measured: Day 1 (baseline) through Day 60

  5. Number of Participants Experiencing Unsolicited Non-Serious Adverse Events

    Unsolicited adverse events were defined as any non-serious clinical adverse events that were not collected as clinical outcome measures and resulted in either modification in the administration of study drug or discontinuation of the study drug.

    Measured: Day 1 (baseline) through Day 60

  6. Time to First Negative Viral Load

    Time (in days) from randomization until the first study day the participant had either a negative result or a result less than the lower limit of quantitation (LLOQ) for the viral load test type (Norovirus GII or Norovirus GI) that they initially tested positive for at baseline. Participants were analyzed for the viral load test type (Norovirus GII or Norovirus GI) that they tested positive for at baseline (Day 1).

    Measured: Day 1 (baseline) and Day 180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2018
  2. Study start15 Oct 2018
  3. Primary completion24 Aug 2021
  4. Study completion24 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03395405
Sponsor's protocol ID
16-0092
Status last verified
25 Jun 2021
First submitted
4 Jan 2018
Last updated
21 May 2025
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Boutin CA, Callegari M, Florescu D, Nguyen MH, Kaul D, Avery R, Chong P, Fisher C, Limaye AP, Clough L, Pergam SA, Green M, Michaels MG, Danziger-Isakov LA, Angarone M, Keefer L, Daud A, Lorenzo-Redondo R, Tan M, Ison MG. A phase 2 multicenter, 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. Am J Transplant. 2026 Sep;26(9):2169-2181. doi: 10.1016/j.ajt.2026.04.010. Epub 2026 May 22.

    PubMed 42177030
  • Shawar S, Concepcion BP. A Gut-Wrenching Infection: Norovirus in a Kidney Transplant Recipient. Clin J Am Soc Nephrol. 2023 Sep 1;18(9):1231-1233. doi: 10.2215/CJN.0000000000000243. Epub 2023 Jun 29. No abstract available.

    PubMed 37382971

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nitazoxanide in people with Gastroenteritis Norovirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Initial Clinical Resolution of Norovirus Symptoms (time frame: 48 hours through Day 180). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03395405, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2025.

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