Evaluation of the Effect of 3HP vs Periodic 3HP vs 6H in HIV-Positive Individuals

NCT02980016 | Completed Phase 3 DMC

• 1 other identifier: 3HP-AUR1-1-170
• Study Type: interventional
• Target: 4,027
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a parallel, two part, open label, individually randomized, pragmatic trial among HIV-positive individuals. Part A compares a single round of weekly high dose rifapentine plus isoniazid for three months (3HP) to six months of daily isoniazid (6H). Part B compares periodic 3HP (p3HP) to a single round of 3HP.

Conditions

Tuberculosis; HIV

Outcome Measures

Primary Outcomes (2)

• Treatment completion (part A)

  Number of participants without evidence of active TB at enrollment who complete treatment, defined as: Proportion of participants in 3HP group self-reporting treatment completion of ≥11 doses in a 16-week period ; Proportion or participants in 6H group self-reporting treatment completion of ≥167 doses over an 34 week (8-month) period

  1 year

• TB incidence (part B)

  Number of participants without evidence of active TB at enrollment who are diagnosed with active TB meeting the definition: Confirmed tuberculosis: Culture-positive, Xpert MTB/RIF-positive, or smear-positive for M. tuberculosis from any site in adults and children OR Clinical tuberculosis: Started on treatment for TB in adults and children

  2 years

Secondary Outcomes (10)

• TB incidence (part A)

  1 year

• All-cause mortality (part A)

  1 year

• Permanent discontinuation of therapy due to treatment-related adverse events (part A)

  1 year

• TB incidence (part B)

  1 year

• Treatment completion (part B)

  2 years

Other Outcomes (3)

• IGRA conversions (part A)

  1 year

• IGRA reversions (part A)

  1 year

• Incidence of TB resistant to isoniazid and/or rifapentine

  2 years

Study Arms (3)

3HP (rifapentine + isoniazid)

ACTIVE COMPARATOR

Once weekly rifapentine (at a dose of 900 mg) plus isoniazid (at a dose of 900 mg), (with adjustment for participants weighing ≤50 kg) given for 12 weeks in Study Year 1

Drug: rifapentine + isoniazid

p3HP (rifapentine + isoniazid)

ACTIVE COMPARATOR

Once weekly rifapentine (at a dose of 900 mg) plus isoniazid (at a dose of 900 mg), (with adjustment for participants weighing ≤50 kg) given for 12 weeks in Study Years 1 and 2

Drug: rifapentine + isoniazid

6H

ACTIVE COMPARATOR

Daily self-administered isoniazid (at a dose of 300 mg/daily) (with adjustment for participants weighing ≤24 kg) given for 26 weeks (6 months) in Study Year 1

Drug: Isoniazid

Interventions

rifapentine + isoniazid DRUG

Rifapentine + isoniazid Once weekly rifapentine (at a dose of 900 mg) plus isoniazid (at a dose of 900 mg), with adjustment for participants weighing ≤50 kg

Also known as: Priftin (rifapentine)

3HP (rifapentine + isoniazid); p3HP (rifapentine + isoniazid)

Isoniazid DRUG

Daily self-administered isoniazid (at a dose of 300 mg/daily), with adjustment for participants weighing ≤24 kg

Also known as: Winthrop (isoniazid)

6H

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• At least two years of age
• Known HIV infection
• Antiretroviral therapy (ART) ineligible or on ART for ≥3 months

You may not qualify if:

• Confirmed or suspected TB disease
• Likely to move from the study area during the study period
• Known exposure to TB cases with known or suspected resistance to isoniazid or rifampicin in the source case
• TB treatment within the past year
• TB preventive therapy within the last year
• Sensitivity or intolerance to isoniazid or rifamycins
• Suspected acute hepatitis or known chronic liver disease
• ALT/AST \>5 times the upper limit of normal (regardless of symptoms of hepatitis)
• Pregnancy or breastfeeding
• Women of childbearing potential who are unable or unwilling to use contraception
• Self-reported alcohol use exceeding 28 units per week for men, or 21 units for women

Sponsors & Collaborators

• The Aurum Institute NPC: lead
• Aurum Institute: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Johns Hopkins University: collaborator

Study Sites (1)

The Aurum Institute NPC

Johannesburg, Gauteng, 2193, South Africa

Location

Related Publications (6)

• Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Weis SE, Weiner M, Wing D, Conde MB, Bozeman L, Horsburgh CR Jr, Chaisson RE; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8;365(23):2155-66. doi: 10.1056/NEJMoa1104875.

  PMID: 22150035 BACKGROUND

• Sterling TR, Moro RN, Borisov AS, Phillips E, Shepherd G, Adkinson NF, Weis S, Ho C, Villarino ME; Tuberculosis Trials Consortium. Flu-like and Other Systemic Drug Reactions Among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study. Clin Infect Dis. 2015 Aug 15;61(4):527-35. doi: 10.1093/cid/civ323. Epub 2015 Apr 22.

  PMID: 25904367 BACKGROUND

• Sterling TR, Benson CA, Shang N. Tolerability among HIV-infected persons of three months of once-weekly rifapentine + INH (3HP) vs. 9 months of daily INH (9H) for treatment of latent tuberculosis infection. In: International AIDS Society Conference. Washington, DC.; 2012.

  BACKGROUND

• Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, McIntyre JA, Gray GE, Chaisson RE. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011 Jul 7;365(1):11-20. doi: 10.1056/NEJMoa1005136.

  PMID: 21732833 BACKGROUND

• Villarino ME, Scott NA, Weis SE, Weiner M, Conde MB, Jones B, Nachman S, Oliveira R, Moro RN, Shang N, Goldberg SV, Sterling TR; International Maternal Pediatric and Adolescents AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr. 2015 Mar;169(3):247-55. doi: 10.1001/jamapediatrics.2014.3158.

  PMID: 25580725 BACKGROUND

• Churchyard G, Cardenas V, Chihota V, Mngadi K, Sebe M, Brumskine W, Martinson N, Yimer G, Wang SH, Garcia-Basteiro AL, Nguenha D, Masilela L, Waggie Z, van den Hof S, Charalambous S, Cobelens F, Chaisson RE, Grant AD, Fielding KL; WHIP3TB Study Team. Annual Tuberculosis Preventive Therapy for Persons With HIV Infection : A Randomized Trial. Ann Intern Med. 2021 Oct;174(10):1367-1376. doi: 10.7326/M20-7577. Epub 2021 Aug 24.

  PMID: 34424730 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

rifapentine; Isoniazid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Gavin Churchyard, MBBCh, PhD

  Aurum Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2016
• First Posted: December 2, 2016
• Study Start: November 1, 2016
• Primary Completion: October 18, 2019
• Study Completion: October 18, 2019
• Last Updated: October 30, 2019

Record last verified: 2019-10

Locations

ZA (1)