Isoniazid Plus Antiretroviral Therapy to Prevent Tuberculosis in HIV-infected Persons

NCT00463086 | Completed DMC

• 1 other identifier: HAARTIPT07
• Study Type: interventional
• Target: 1,368
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether isoniazid can safely (and further) reduce the risk of tuberculosis in HIV infected people receiving HAART.

Conditions

Tuberculosis; Latent Tuberculosis Infection; HIV Infections

Keywords

Tuberculosis; TB; Mycobacteria; HIV; Human immunodeficiency virus; Latent tuberculosis infection; HAART; Highly active anti-retroviral therapy; Isoniazid preventive therapy; INH; Opportunistic infections; HIV-1; Treatment Experienced; AIDS; Mycobacterium Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Rate of development of TB (microbiologically confirmed TB or highly probable TB) during the 36 month risk period

  Patients are assessed for TB one two monthly at each ART re-fill appointment

Secondary Outcomes (5)

• Rate of drug toxicity (specifically, peripheral neuropathy, hepatitis +/-raised ALT grade III or worse and allergic rashes grade III or worse

  during the intervention period (ALT determined at baseline, 1, 2 and 3 months and then 3-monthly. the last safety determination is at 12 months post initiation of the study drug)

• Proportions adhering to study drug and HAART at the end of each study year as measured by pharmacy refills

  1 month to two monthly, depending on the individual patient's clinic appointment

• Rate of development of INH monoresistance during the 36 month risk period.

  36 months

• Death

  36 months

• Worsening ART outcomes (virological and immunological failure)

  CD4+count and viral load are assessed as per clinic protocol (6 monthly post ART initiation)

Study Arms (2)

1.Isoniazid (INH)

EXPERIMENTAL

A self-administered daily dose of 5mg/kg of Isoniazid (300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg)

Drug: isoniazid

2. Placebo

PLACEBO COMPARATOR

A self-administered daily dose of 5mg/kg of placebo for 12months (300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg)

Drug: Placebo

Interventions

isoniazid DRUG

A self-administered daily dose of 5mg/kg of Isoniazid or placebo for 12months(300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg)

1.Isoniazid (INH)

Placebo DRUG

A self-administered dose of 5mg/kg of placebo (300mg if weight is more than or equal to 50kg and 200mg if weight is less than 50kg)

2. Placebo

Eligibility Criteria

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

You may qualify if:

• Male and female attendees (age ≥18yo) of the Ubuntu HIV and ARV Clinic identified as eligible for the ARV programme will be invited to participate.
• Willingness to participate
• Able to engage in informed consent procedures

You may not qualify if:

• Evidence of active TB or suspicion of active TB as determined by a symptoms screening algorithm.
• Current or previous treatment of latent TB infection since HIV infection (any duration)
• Current treatment with fluoroquinolones or other antibiotics with significant anti-tuberculous activity currently being used to treat TB in South Africa
• Past reaction/intolerance to INH.
• Acute hepatitis or existing Grade III-IV peripheral neuropathy.
• Pregnancy or \< 6weeks post-partum period (Due to increased risk of hepatotoxicity).
• Grade III or higher baseline abnormal liver function. (Note: toxicity grades are all according to ACTG toxicity tables for persons on ART).

Sponsors & Collaborators

• University of Cape Town: lead
• Medecins Sans Frontieres, Netherlands: collaborator
• Imperial College London: collaborator
• Johns Hopkins University: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (1)

Ubuntu Clinic,Site B Khayelitsha

Cape Town, Western Cape, South Africa

Location

Related Publications (1)

• Rangaka MX, Wilkinson RJ, Boulle A, Glynn JR, Fielding K, van Cutsem G, Wilkinson KA, Goliath R, Mathee S, Goemaere E, Maartens G. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind, placebo-controlled trial. Lancet. 2014 Aug 23;384(9944):682-90. doi: 10.1016/S0140-6736(14)60162-8. Epub 2014 May 13.

  PMID: 24835842 DERIVED

MeSH Terms

Conditions

Tuberculosis; Latent Tuberculosis; HIV Infections; Mycobacterium Infections; Acquired Immunodeficiency Syndrome; Opportunistic Infections

Interventions

Isoniazid

Condition Hierarchy (Ancestors)

Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Gary Maartens (overall PI), FCP

  University of Cape Town

  PRINCIPAL INVESTIGATOR

• Eric Goemaere (co-investigator), MBBS

  Medecins Sans Frontieres, Netherlands

  STUDY DIRECTOR

• Molebogeng X Rangaka (Lead Investigator), MBChB

  University of Cape Town

  STUDY DIRECTOR

• Gilles van Cutsem co-investigator), MBBS

  Medecins Sans Frontieres, Netherlands

  STUDY DIRECTOR

• Andrew Boulle co-investigator), FCP

  University of Cape Town

  STUDY DIRECTOR

• Robert J Wilkinson (PI:Immunology Studies), FRCP

  Wellcome Trust

  STUDY DIRECTOR

• Shahied Mathee (Ubuntu PMO), MBChB

  Provincial Government of Western Cape

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 19, 2007
• First Posted: April 20, 2007
• Study Start: November 1, 2007
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: July 17, 2012

Record last verified: 2012-07

Locations

ZA (1)