A 14 Day Early Bactericidal Activity Study of Nitazoxanide for the Treatment of Tuberculosis

NCT02684240 | Completed Phase 2 DMC

• 1 other identifier: 1302013616
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to determine if Nitazoxanide (NTZ) will cause a significant decrease in the number of M. tuberculosis bacteria in sputum after 14 days of treatment. The study is being conducted at the GHESKIO Centers in Port au Prince Haiti

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• time to positivity (TTP)

  To assess the change in time in hours to positive (TTP) signal in an automated liquid media culture system (BACTEC MGIT 960, Becton Dickinson) in participants receiving NTZ over 14 days

  first 14 days of anti-tuberculosis therapy

Secondary Outcomes (11)

• Number of participants with treatment-related adverse events as determined by DAIDS toxicity tables

  first 14 days of anti-tuberculosis therapy

• Maximum plasma concentration of NTZ

  first 14 days of anti-tuberculosis therapy

• Most probable number of M tuberculosis in 1 ml of sputum

  first 14 days of anti-tuberculosis therapy

• First-line drug susceptibility (DST) of Mycobacterium tuberculosis via Mycobacterial Growth Indicator System (MGIT)

  first 14 days of anti-tuberculosis therapy

• Quantification of change in urine metabolites and correlation with change in TTP

  first 14 days of anti-tuberculosis therapy

Study Arms (2)

Nitazoxanide

EXPERIMENTAL

Participants with drug-sensitive tuberculous randomized to the NTZ arm will receive nitazoxanide 1000 mg po twice daily for 14 days. After this time point, participants will be switched to WHO standard tuberculosis therapy with isoniazid, rifampin, pyrazinamide and ethambutol.

Drug: Nitazoxanide

Control

OTHER

Participants with drug-sensitive tuberculosis randomized to the standard therapy arm will receive WHO standard tuberculosis therapy involving isoniazid 300 mg po daily, rifampin 600 mg po daily, pyrazinamide 25 mg/kg po daily and ethambutol 15 mg/kg po daily.

Other: Control

Interventions

Nitazoxanide DRUG

nitazoxanide 1000 mg orally twice daily with food for 14 days

Also known as: Nizonide, Alinia

Nitazoxanide

Control OTHER

The control arm will receive WHO standard therapy for tuberculosis with isoniazid, rifampin, pyrazinamide, and ethambutol

Control

Eligibility Criteria

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

You may qualify if:

• Men and women ages 18 - 65
• Diagnosed with pulmonary tuberculosis via: sputum-microscopy smear-positive (2+ or 3+) within 14 days plus Sputum GeneXpert positive within 14 days plus Chest radiograph consistent with M. tuberculosis within 14 days
• TB treatment naïve at time of enrollment
• Bodyweight \> 40kg
• Negative HIV test within 30 days
• Able to complete activities of daily living (ADLs)
• All participants must agree not to participate in a conception process (i.e. active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization)
• All female participants must agree to use barrier methods such as condoms as well as hormonal contraception for dual prophylaxis.
• Able to give informed consent and demonstrate understanding of this study and willingness to participate in this study
• Willing to be hospitalized for 2 weeks

You may not qualify if:

• Pregnancy
• Evidence of complications of M. tuberculosis such as hemoptysis or shortness of breath
• Extrapulmonary manifestations of M. tuberculosis
• History of prior active tuberculosis
• Evidence of rifampin resistance via GeneXpert
• Previous diagnosis of diabetes or suggestion of impaired glucose metabolism via random plasma glucose
• Previous diagnosis of HIV by any rapid HIV test or by ELISA
• Any of the following lab abnormalities: Creatinine \> 1.5 times the ULN; Random glucose \> 2 times the ULN; ALT, AST, or alkaline phosphatase \> 2 times the ULN; Hemoglobin \< 7.5 g/dL
• Any participant currently taking antimycobacterial therapy or within the past 30 days
• Any concomitant illness that could compromise patient safety in this trial such as renal failure, chronic liver disease or alcoholic dependency
• Enrolled in another clinical trial

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Les Centres GHESKIO

Port-au-Prince, Haiti

Location

Related Publications (5)

• de Carvalho LP, Lin G, Jiang X, Nathan C. Nitazoxanide kills replicating and nonreplicating Mycobacterium tuberculosis and evades resistance. J Med Chem. 2009 Oct 8;52(19):5789-92. doi: 10.1021/jm9010719.

  PMID: 19736929 BACKGROUND

• Stockis A, De Bruyn S, Gengler C, Rosillon D. Nitazoxanide pharmacokinetics and tolerability in man during 7 days dosing with 0.5 g and 1 g b.i.d. Int J Clin Pharmacol Ther. 2002 May;40(5):221-7. doi: 10.5414/cpp40221.

  PMID: 12051574 BACKGROUND

• Shigyo K, Ocheretina O, Merveille YM, Johnson WD, Pape JW, Nathan CF, Fitzgerald DW. Efficacy of nitazoxanide against clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2013 Jun;57(6):2834-7. doi: 10.1128/AAC.02542-12. Epub 2013 Mar 18.

  PMID: 23507275 BACKGROUND

• Walsh KF, McAulay K, Lee MH, Vilbrun SC, Mathurin L, Jean Francois D, Zimmerman M, Kaya F, Zhang N, Saito K, Ocheretina O, Savic R, Dartois V, Johnson WD, Pape JW, Nathan C, Fitzgerald DW. Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e01956-19. doi: 10.1128/AAC.01956-19. Print 2020 Apr 21.

  PMID: 32071052 RESULT

• Wipperman MF, Bhattarai SK, Vorkas CK, Maringati VS, Taur Y, Mathurin L, McAulay K, Vilbrun SC, Francois D, Bean J, Walsh KF, Nathan C, Fitzgerald DW, Glickman MS, Bucci V. Gastrointestinal microbiota composition predicts peripheral inflammatory state during treatment of human tuberculosis. Nat Commun. 2021 Feb 18;12(1):1141. doi: 10.1038/s41467-021-21475-y.

  PMID: 33602926 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

nitazoxanide

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Daniel W Fitzgerald, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

• Carl Nathan, MD

  Weill Medical College of Cornell University

  STUDY CHAIR

• Jean William Pape, MD

  Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2016
• First Posted: February 17, 2016
• Study Start: February 1, 2016
• Primary Completion: April 11, 2018
• Study Completion: April 11, 2018
• Last Updated: August 5, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share

Locations

HA (1)