NNITS-Nitazoxanide for Norovirus in Transplant Patients Study

NCT03395405 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 16-0092
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 12

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.

Conditions

Gastroenteritis Norovirus

Keywords

Efficacy; Hematopoietic Stem Cell; Nitazoxanide; Norovirus; Prospective, Randomized, Double-Blind Study; Safety; Solid Organ Transplant Recipients; Treatment

Outcome Measures

Primary Outcomes (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.

  48 hours through Day 180

Secondary Outcomes (6)

• Number of Participants Experiencing Laboratory Adverse Events (AEs)

  Day 1 (baseline) through Day 60

• Change in Viral Titer (Day 1 to Day 180)

  Day 1 (baseline) and Day 180

• Number of Participants Reporting Hospitalization

  Day 1 (baseline) through Day 60

• Number of Participants Reporting Protocol-Specified SAEs

  Day 1 (baseline) through Day 60

• Number of Participants Experiencing Unsolicited Non-Serious Adverse Events

  Day 1 (baseline) through Day 60

Study Arms (2)

Nitazoxanide Arm

EXPERIMENTAL

500 mg (one tablet) nitazoxanide by mouth twice daily with food for 56 consecutive doses. N=80

Drug: Nitazoxanide

Placebo Arm

PLACEBO COMPARATOR

Placebo (one tablet) by mouth twice daily with food for 56 consecutive doses. N=80

Other: Placebo

Interventions

Nitazoxanide DRUG

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

Nitazoxanide Arm

Placebo OTHER

One tablet twice daily with food for 56 consecutive doses

Placebo Arm

Eligibility Criteria

• Age: 12 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (12)

Northwestern University - Comprehensive Transplant Center

Chicago, Illinois, 60611-2927, United States

Location

University of Kansas Medical Center - Infectious Diseases

Kansas City, Kansas, 66160-8500, United States

Location

Johns Hopkins Hospital - Medicine - Infectious Diseases

Baltimore, Maryland, 21287-0005, United States

Location

University of Michigan School of Public Health - Epidemiology

Ann Arbor, Michigan, 48109-2029, United States

Location

University of Michigan - Infectious Disease Clinic at Taubman Center

Ann Arbor, Michigan, 48109, United States

Location

University of Nebraska Medical Center - Infectious Diseases

Omaha, Nebraska, 68198-5400, United States

Location

Cincinnati Children's Hospital Medical Center Vaccine Research Center

Cincinnati, Ohio, 45229-3039, United States

Location

University of Pittsburgh - Medicine - Infectious Diseases

Pittsburgh, Pennsylvania, 15213-3403, United States

Location

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

Pittsburgh, Pennsylvania, 15224-1529, United States

Location

University of Texas Southwestern Medical Center - Internal Medicine Subspecialties Clinic

Dallas, Texas, 75390-8884, United States

Location

Fred Hutchinson Cancer Research Center - Vaccine and Infectious Diseases

Seattle, Washington, 98109-4433, United States

Location

University of Washington - Medicine

Seattle, Washington, 98195-7110, United States

Location

Related Publications (1)

• 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.

  PMID: 37382971 DERIVED

MeSH Terms

Interventions

nitazoxanide

Results Point of Contact

• Title: Michael G Ison
• Organization: Northwestern University Feinberg School of Medicine

mgison@northwestern.edu

3126954186

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: January 10, 2018
• Study Start: October 15, 2018
• Primary Completion: August 24, 2021
• Study Completion: August 24, 2021
• Last Updated: May 21, 2025
• Results First Posted: October 24, 2022

Record last verified: 2021-06-25

Locations

US (12)