Nitazoxanide Versus Placebo for the Treatment of Hospitalized Subjects With Severe Acute Respiratory Illness

NCT ID: NCT02057757

Last Updated: 2018-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2018-01-31

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.

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.

Conditions

Severe Acute Respiratory Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Nitazoxanide

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

NTZ; PCB

Eligibility 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)

• Minimum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mexican Emerging Infectious Diseases Clinical Research Network

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lourdes Guerrero Almeida, M.D.

Role: STUDY_CHAIR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Ana Gamiño, M.D.

Role: STUDY_CHAIR

Hospital Infantil de Mexico Federico Gomez

Arturo Galindo Fraga, M.D.

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Sarbelio Moreno, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hospital Infantil de Mexico Federico Gomez

Javier Araujo Melendez, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hospital Central "Dr. Ignacio Morones Prieto"

Alejandra Ramirez Venegas, M.D.

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Enfermedades Respiratorias

Beatriz Llamosas Gallardo, M.D.

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Pediatria

Yuri Roldan Aragon, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hospital General Dr. Aurelio Valdivies

Locations

Instituto Nacional de Pediatria

Coyoacán, , Mexico

Hospital General Dr. Aurelio Valdivieso

Oaxaca City, , Mexico

Hospital Central Dr. Ignacio Morones Prieto

San Luis Potosí City, , Mexico

Hospital Infantil de Mexico Federico Gomez

Tamaulipas, , Mexico

Instituto Nacional de Ciencias medicas y Nutricion Salvador Zubiran

Tlalpan, , Mexico

Instituto Nacional de Enfermedades Respiratorias

Tlalpan, , Mexico

Countries

Mexico

References

Gamino-Arroyo AE, Guerrero ML, McCarthy S, Ramirez-Venegas A, Llamosas-Gallardo B, Galindo-Fraga A, Moreno-Espinosa S, Roldan-Aragon Y, Araujo-Melendez J, Hunsberger S, Ibarra-Gonzalez V, Martinez-Lopez J, Garcia-Andrade LA, Kapushoc H, Holley HP, Smolskis MC, Ruiz-Palacios GM, Beigel JH; Mexico Emerging Infectious Diseases Clinical Research Network (LaRed). Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness. Clin Infect Dis. 2019 Nov 13;69(11):1903-1911. doi: 10.1093/cid/ciz100.

Reference Type: DERIVED

PMID: 30753384 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

NTZ-SARI

Identifier Type: -

Identifier Source: org_study_id