Evaluating the Safety, Effectiveness, and Tolerability of Nitazoxanide in Addition to Standard Care for the Treatment of Severe Acute Respiratory Illness in People Who Are Hospitalized

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Collaborator:
Mexican Emerging Infectious Diseases Clinical Research Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02057757
First received: February 5, 2014
Last updated: NA
Last verified: February 2014
History: No changes posted
  Purpose

Respiratory viruses are a significant cause of hospitalization for respiratory tract infections. This study will evaluate the safety, effectiveness, and tolerability of nitazoxanide (NTZ) in treating severe acute respiratory illness (SARI) in people who are hospitalized.


Condition Intervention Phase
Severe Acute Respiratory Illness
Drug: Nitazoxanide (NTZ)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind Phase 2 Study Comparing the Efficacy, Safety, and Tolerability of Nitazoxanide Versus Placebo in Addition to Standard Care for the Treatment of Hospitalized Subjects With Severe Acute Respiratory Illness

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Duration of hospitalization (days and hours) [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants hospitalized on Days 3, 7, 14, and 28 [ Time Frame: Measured through Day 28 ] [ Designated as safety issue: Yes ]
  • Date of death [ Time Frame: Measured through participants' date of death ] [ Designated as safety issue: Yes ]
  • Number of participants who experienced clinical symptoms [ Time Frame: Measured through Day 28 ] [ Designated as safety issue: Yes ]
    Measured daily through Day 14 and then again on Day 28

  • Participants' temperature readings, as recorded in participant diaries [ Time Frame: Measured through Day 28 ] [ Designated as safety issue: Yes ]
    Measured daily through Day 14 and then again on Day 28

  • Number of participants who require oxygen use [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ] [ Designated as safety issue: Yes ]
  • Date of admission to intensive care unit (ICU) and discharge from ICU, if applicable [ Time Frame: Measured through Day 28 or participants' last day in the ICU ] [ Designated as safety issue: Yes ]
  • Date of intubation/extubation, if applicable [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ] [ Designated as safety issue: Yes ]
  • Presence of complications during study (pneumonia, respiratory failure requiring mechanical ventilation, acute respiratory distress syndrome [ARDS], sepsis, or bronchiolitis) [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ] [ Designated as safety issue: Yes ]
  • Answers (yes or no) to global assessment questions [ Time Frame: Measured through Day 28 ] [ Designated as safety issue: Yes ]
    Measured daily through Day 14 and then again on Day 28

  • Number of participants using antibiotics/antivirals during hospitalization [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ] [ Designated as safety issue: Yes ]
  • Number of participants who are re-hospitalized within 28 days [ Time Frame: Measured through Day 28 ] [ Designated as safety issue: Yes ]
  • Use of systemic corticosteroids [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ] [ Designated as safety issue: Yes ]
  • Presence of virus on nasopharyngeal (NP) swab at Day 3 (same virus as Day 0) [ Time Frame: Measured through Day 3 ] [ Designated as safety issue: No ]
  • Number of participants reporting adverse events (AEs) [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ] [ Designated as safety issue: Yes ]
  • Number of participants reporting serious adverse events (SAEs) [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ] [ Designated as safety issue: Yes ]
  • Chemistry and hematologic laboratory assessments on Days 3 and 28 [ Time Frame: Measured through Day 28 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 290
Study Start Date: February 2014
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nitazoxanide (NTZ)
Participants will receive NTZ for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ; participants 12 years and older will receive NTZ tablets.
Drug: Nitazoxanide (NTZ)

Participants 1 to 3 years old: 5 mL oral suspension (100 mg NTZ) every 12 hours for 5 days.

Participants 4 to 11 years old: 10 mL oral suspension (200 mg NTZ) every 12 hours for 5 days.

Participants 12 years and older: two 300-mg NTZ tablets orally twice daily for 5 days.

Placebo Comparator: Placebo
Participants will receive placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of placebo; participants 12 years and older will receive placebo tablets.
Drug: Placebo

Participants 1 to 3 years old: 5 mL placebo oral suspension every 12 hours for 5 days.

Participants 4 to 11 years old: 10 mL placebo oral suspension every 12 hours for 5 days.

Participants 12 years and older: two placebo tablets orally twice daily for 5 days.


Detailed Description:

Respiratory viral infections are one of the most common causes of illness in the world. These infections are major causes of SARI and can lead to severe outcomes, including hospitalization and death. NTZ is a medication that is approved in the United States and Mexico to treat gastrointestinal parasitic diseases. This study will evaluate the use of NTZ to treat SARI. The purpose of this study is to evaluate the safety, effectiveness, and tolerability of NTZ, in combination with standard care, in treating SARI in people who are hospitalized.

Participants will be hospitalized and study entry assessments will include medical assessments, blood collection, and a nasopharyngeal swab or wash. Participants will then be randomly assigned to receive NTZ or placebo for 5 days. Participants younger than 12 years will receive an oral suspension formulation of NTZ or placebo; participants 12 years and older will receive NTZ or placebo tablets. All participants will also receive standard of care treatment for acute severe viral respiratory infections, which may include antibiotics and/or treatment for influenza. They will be discharged from the hospital based on their doctors' recommendations. Participants will record their temperature and symptoms in a daily diary, which will be reviewed by study staff during study visits. Follow-up visits will occur on Days 3, 7, 14, and 28, and may occur as inpatient or outpatient visits. These visits may include the same assessments that occurred at baseline, as well as physical examinations, depending on the visit. Participants who are still hospitalized at Day 28 will be followed by study staff until they are discharged from the hospital.

  Eligibility

Ages Eligible for Study:   12 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent prior to performance or initiation of any study procedures
  • Age greater than or equal to 12 months of age (no upper age limit)
  • Influenza-like illness (ILI), defined as (all of the following):

    • Onset of fever greater than or equal to 38°C (or hypothermia less than 36°C)
    • New or worse cough or sore throat
    • New or worse shortness of breath or difficulty breathing
  • Onset of illness no more than 5 days before screening defined as when the participant experienced at least 1 respiratory symptom, constitutional symptom, or fever
  • Hospitalization for ILI (decision for hospitalization will be up to the individual treating clinician), with anticipated hospitalization for more than 24 hours
  • One of the following to avoid pregnancy:

    • Females who are able to become pregnant (i.e., are not postmenopausal, have not undergone surgical sterilization, and are sexually active with men) must agree to use at least 1 effective form of contraception from the date of informed consent through Day 28 of study
    • Males who have not undergone surgical sterilization and are sexually active with women must agree to use condoms or have a partner use at least 1 effective form of contraception through Day 28 of study

Exclusion Criteria:

  • Women who are pregnant or breastfeeding
  • Clinical suspicion that etiology of illness is primarily bacterial in origin
  • Prior treatment with antivirals (e.g., oseltamivir) for the current illness for more than 24 hours
  • Unable to take oral medications (adults must tolerate tablets, children must tolerate suspension)
  • Unable to tolerate oral food/fluids (absorption is significantly better with food)
  • Prior treatment with any investigational drug therapy within 30 days prior to screening
  • Known sensitivity to NTZ or any of the excipients comprising the NTZ tablets
  • Prior NTZ use within 1 week
  • Self-reported history of chronic kidney disease or impaired renal function (no blood or urine kidney function laboratory testing will be done prior to enrollment, but intent is to exclude disease severe enough to cause estimated creatinine clearance [CrCl] less than 30)
  • Self-reported history of liver disease (no blood laboratory testing will be done prior to enrollment, but intent is to exclude disease severe enough to cause cirrhosis or total bilirubin greater than 2, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] greater than 3 times the upper limit of normal [ULN])
  • Presence of any pre-existing illness that, in the opinion of the investigator, would place the participant at an unreasonably increased risk through participation in this study
  • Participants who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol
  • The onset of SARI occurs after hospitalization
  • Hospitalized for any reason for greater than 48 hours prior to enrollment
  • Participants previously enrolled in this study
  • Prior hospital discharge within 30 days
  • Known chronic respiratory infection (e.g., tuberculosis, atypical mycobacterial infections)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02057757

Sponsors and Collaborators
Mexican Emerging Infectious Diseases Clinical Research Network
Investigators
Principal Investigator: Javier Araujo Melendez Hospital Central "Dr. Ignacio Morones Prieto"
Principal Investigator: Arturo Galindo Fraga Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Principal Investigator: Beatriz Llamosas Gallardo Instituto Nacional De Pediatria
Principal Investigator: Sarbelio Moreno Espinosa Hospital Infantil de Mexico Federico Gomez
Principal Investigator: Alejandra Ramirez Venegas Instituto Nacional De Enfermedades Respiratorias Ismael Cosio Villegas
Principal Investigator: Rafael Valdez Vazquez Hospital General Dr. Manuel Gea Gonzalez
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02057757     History of Changes
Other Study ID Numbers: NTZ-SARI
Study First Received: February 5, 2014
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Nitazoxanide
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014