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Nitazoxanide Versus Placebo for the Treatment of Hospitalized Subjects With Severe Acute Respiratory Illness (NTZ-SARI)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02057757
Recruitment Status : Completed
First Posted : February 7, 2014
Results First Posted : July 31, 2018
Last Update Posted : August 1, 2018
Sponsor:
Collaborator:
Mexican Emerging Infectious Diseases Clinical Research Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
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 or disease Intervention/treatment Phase
Severe Acute Respiratory Illness Drug: Nitazoxanide Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : February 2014
Actual Primary Completion Date : May 2017
Actual Study Completion Date : January 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

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.

Other Name: NTZ

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.

Other Name: PCB




Primary Outcome Measures :
  1. Time to Hospital Discharge [ Time Frame: Measured through Day 28 ]
    The time to hospital discharge measured through Day 28.


Secondary Outcome Measures :
  1. Number of Participants Hospitalized on Days 3, 7, 14, and 28 [ Time Frame: Measured at Day 3, Day 7, Day 14, and Day 28 ]
    The number of study participants (e.g., adults and children) who were hospitalized on Days 3, 7, 14, and 28.

  2. Number of Participants Who Died Within the First 5 Days [ Time Frame: Measured within First 5 Days ]
    Total Deaths of Participants, including Deaths within First 5 Days

  3. Number of Participants Who Experienced Clinical Symptoms [ Time Frame: Measured through Day 28 ]
    Measured daily through Study Day 14 and then again on Study Day 28

  4. Duration of Fever in Study Participants [ Time Frame: Measured each day through Day 14 and on Day 28 ]
    Study participants' duration (hours) of fever measured daily through Day 14 and then again on Day 28. The total duration in hours from the visit when fever was registered for the study participant until the next visit when no fever was registered for the study participant.

  5. Number of Participants Who Require Oxygen Use [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ]
    Number of study participants who require use of supplemental oxygen at time points (e.g., Any time, Day 0, Day 3, Day 7, Day 14, and Day 28)

  6. Number of Study Participants (e.g., Adult and Children) Admitted to the Intensive Care Unit (ICU) by Time Point (Anytime, Day 0, Day 3, Day 7, Day 14, Day 28) [ Time Frame: Measured through Day 28 or participants' last day in the ICU ]
    Number of study participants (e.g., adult and children) admitted to the intensive care unit (ICU) by time point (Anytime, Day 0, Day 3, Day 7, Day 14, Day 28); worst case imputed.

  7. Study Participants (e.g., Adults, Children) Requiring Mechanical Ventilation at Study Time Points (Any Time, Day 0, Day 3, Day 7, Day 14, Day 28) [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ]
    Study participants (e.g., adults, children) requiring mechanical ventilation (e.g., intubation/extubation) at study time points (Any Time, Day 0, Day 3, Day 7, Day 14, Day 28); worst case imputed.

  8. Number of Study Participants With the Presence of Complications (Pneumonia, Respiratory Failure Requiring Mechanical Ventilation, Acute Respiratory Distress Syndrome [ARDS], Sepsis, or Bronchiolitis) During Study [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ]
    Number of study participants (e.g., adults and children) with the presence of a complication (pneumonia, respiratory failure requiring mechanical ventilation, acute respiratory distress syndrome [ARDS], sepsis, or bronchiolitis) during the study .

  9. Duration (Days) Until Affirmative Global Assessment (e.g., Answered Yes) by Study Participants (e.g., Adults, Children) [ Time Frame: Measured daily through Day 14 and on Day 28 ]
    Study participant (e.g., adults and children) answers (e.g., yes) to global assessment questions measured daily through Day 14 and then again on Day 28.

  10. Number of Participants Using Antibiotics/Antivirals During Hospitalization [ Time Frame: Measured through participants' first 5 days of hospitalization ]
    Number of study participants taking an Antibiotic or Anti-Influenza Antiviral during first 5 days of hospitalization.

  11. Number of Participants Who Are Re-hospitalized Within 28 Days [ Time Frame: Measured through Day 28 ]
    Number of study participants (e.g., adults and children) who were re-hospitalized within 28 days (e.g., days from randomization).

  12. Use of Systemic Corticosteroids [ Time Frame: Measured within First 5 Days ]
    Number of study participants taking Systemic Steroids during first 5 days.

  13. Presence of Virus on Nasopharyngeal (NP) Swab at Day 3 (Same Virus as Day 0) [ Time Frame: Measured through Day 3 ]
    Study participants with Detectable Virus on nasopharyngeal (NP) swab at Baseline and at Day 3.

  14. Number of Participants Reporting Adverse Events (AEs) [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ]
    Number of study participants with at least one Adverse Event During Study Duration

  15. Number of Participants Reporting Serious Adverse Events (SAEs) [ Time Frame: Measured through Day 28 or participants' last day of hospitalization ]
    Number of study participants (e.g., adults and children) reporting at least one serious adverse events (SAEs).

  16. Chemistry Laboratory Assessments (Creatinine, Total Bilirubin) on Days 3, 7, and 28 [ Time Frame: Measured on Day 3, Day, 7 and Day 28 ]
    Laboratory values for chemistry laboratory assessments (e.g., Creatinine and Total Bilirubin) on Days 3, 7, and 28.

  17. Chemistry Laboratory Assessments (ALT, AST, LDH) on Days 3, 7, and 28 [ Time Frame: Measured on Day 3, Day 7, and Day 28 ]
    Chemistry laboratory assessments (e.g., ALT, AST, and LDH) on Days 3, 7, and 28.

  18. Chemistry Laboratory Assessment (CRP) on Days 3, 7, and 28 [ Time Frame: Measured on Day 3, Day, 7 and Day 28 ]
    Lab Values for chemistry laboratory assessment (e.g., CRP) on Days 3, 7, and 28.

  19. Hematologic Laboratory Assessments (Neutrophils, Lymphocytes, Eosinophils, and Hematocrit) on Days 3, 7, and 28 [ Time Frame: Measured on Day 3, Day, 7 and Day 28 ]
    Hematology laboratory assessments (e.g., Neutrophils, Lymphocytes, Eosinophils, and Hematocrit) on Days 3, 7, and 28.

  20. Hematologic Laboratory Assessment (Hemoglobin) on Days 3, 7, and 28 [ Time Frame: Measured on Day 3, Day, 7 and Day 28 ]
    Hematology laboratory assessment (e.g., Hemoglobin) on Days 3, 7, and 28.

  21. Hematologic Laboratory Assessments (WBC, Platelets) on Days 3, 7, and 28 [ Time Frame: Measured on Day 3, Day, 7 and Day 28 ]
    Lab values for hematology laboratory assessments (e.g., WBC and Platelets) on Days 3, 7, and 28.



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.


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Ages Eligible for Study:   12 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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)

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): NCT02057757


Locations
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Mexico
Instituto Nacional de Pediatria
Coyoacan, Mexico, 04530
Hospital General Dr. Aurelio Valdivieso
Oaxaca, Mexico, 68050
Hospital Central Dr. Ignacio Morones Prieto
San Luis Potosi, Mexico, 78240
Hospital Infantil de Mexico Federico Gomez
Tamaulipas, Mexico, 06720
Instituto Nacional de Ciencias medicas y Nutricion Salvador Zubiran
Tlalpan, Mexico, 14000
Instituto Nacional de Enfermedades Respiratorias
Tlalpan, Mexico, 14000
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Mexican Emerging Infectious Diseases Clinical Research Network
Investigators
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Study Chair: Lourdes Guerrero Almeida, M.D. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Chair: Ana Gamiño, M.D. Hospital Infantil de Mexico Federico Gomez
Principal Investigator: Arturo Galindo Fraga, M.D. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Principal Investigator: Sarbelio Moreno, M.D. Hospital Infantil de Mexico Federico Gomez
Principal Investigator: Javier Araujo Melendez, M.D. Hospital Central "Dr. Ignacio Morones Prieto"
Principal Investigator: Alejandra Ramirez Venegas, M.D. Instituto Nacional de Enfermedades Respiratorias
Principal Investigator: Beatriz Llamosas Gallardo, M.D. Instituto Nacional de Pediatria
Principal Investigator: Yuri Roldan Aragon, M.D. Hospital General Dr. Aurelio Valdivies
  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
Statistical Analysis Plan  [PDF] October 17, 2017
Study Protocol  [PDF] September 12, 2016

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02057757    
Other Study ID Numbers: NTZ-SARI
First Posted: February 7, 2014    Key Record Dates
Results First Posted: July 31, 2018
Last Update Posted: August 1, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Nitazoxanide
Antiparasitic Agents
Anti-Infective Agents