Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Nitazoxanide for the Treatment of Norovirus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03395405
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : April 15, 2019
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 duration is 60 months and subject participation duration is 6 months. A total of 160 subjects greater than or equal to 12 years of age will be selected. Upon enrollment in the study, subjects will be randomized into two treatment groups: active nitazoxanide and placebo. 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 and study visits on study Day 1, 7, 14, 21, and 28; Longitudinal Monitoring Phase which will include telephone call on Day 35 study visits on study Day 60, 120 and 180 days. 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 duration is 60 months and subject participation duration is 6 months. A total of 160 subjects greater than or equal to 12 years of age will be selected. Upon enrollment in the study, subjects will be randomized into two treatment groups: active nitazoxanide and placebo. 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 and study visits on study Day 1, 7, 14, 21, and 28; Longitudinal Monitoring Phase which will include telephone call on Day 35 study visits on study Day 60, 120 and 180 days. 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.

Layout table for study information
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 28 consecutive days. N=80
Drug: Nitazoxanide
One 500 mg tablet twice daily with food for 28 consecutive days

Placebo Comparator: Placebo Arm
Placebo (one tablet) by mouth twice daily with food for 28 consecutive days. N=80
Other: Placebo
One tablet twice daily with food for 28 consecutive days




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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 for Norovirus within 7 days of enrollment that is obtained as part of routine clinical care using the local Norovirus testing available at the site.
  4. Active GI symptoms (diarrhea, or vomiting) that, in the opinion of the PI, are secondary to Norovirus.
  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.
  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.
  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
Layout table for location contacts
Contact: Michael Grundel Ison 13126954186 mgison@northwestern.edu

Locations
Layout table for location information
United States, Alabama
University of Alabama Hospital - Infectious Diseases Not yet recruiting
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 Not yet recruiting
Baltimore, Maryland, United States, 21287-0005
United States, Michigan
University of Michigan - Infectious Disease Clinic at Taubman Center Not yet 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)

Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03395405     History of Changes
Other Study ID Numbers: 16-0092
HHSN272201600016C
First Posted: January 10, 2018    Key Record Dates
Last Update Posted: April 15, 2019
Last Verified: May 23, 2018

Layout table for additional information
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
Nitazoxanide
Norovirus
Safety
Treatment

Additional relevant MeSH terms:
Layout table for MeSH terms
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Nitazoxanide
Antiparasitic Agents
Anti-Infective Agents