NCT00330304

Brief Summary

The study involves use of isoniazid and cotrimoxazole as strategies for preventing infections in HIV-infected children and reducing mortality. Cotrimoxazole is well known to reduce mortality and infections in HIV-infected children and is currently the recommended standard of care. However, isoniazid has only been studied in HIV-infected adults (in whom it has been shown to substantially reduce the incidence of tuberculosis). In a randomised controlled study of isoniazid in HIV-infected children, the investigators found that INH reduced mortality and tuberculosis incidence in excess of 50%; the data safety monitoring board recommended termination of the placebo arm given the beneficial effects of INH. The investigators therefore aim to follow-up these children to compare the long term impact of two different INH and CTX preventive regimens (daily versus thrice weekly) on morbidity, mortality, adherence and incidence of adverse reactions. The investigators also aim to investigate the efficacy, safety and tolerability of INH compared with placebo for prevention of TB in children receiving HAART as the benefit in this group is unknown.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
450

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jan 2003

Longer than P75 for phase_3

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2003

Completed
3.4 years until next milestone

First Submitted

Initial submission to the registry

May 24, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 26, 2006

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 15, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 15, 2011

Completed
Last Updated

April 22, 2019

Status Verified

April 1, 2019

Enrollment Period

8.9 years

First QC Date

May 24, 2006

Last Update Submit

April 18, 2019

Conditions

Tuberculosis

Keywords

TuberculosisChildHIVprophylaxismortality

Outcome Measures

Primary Outcomes (2)

  • TB incidence

    Jan 2003 to July 2011

  • Mortality

    Jan 2003 to July 2011

Secondary Outcomes (4)

  • intercurrent infections

    Jan 2003 to July 2011

  • adherence

    Jan 2003 to July 2011

  • adverse events

    Jan 2003 to July 2011

  • antimicrobial resistance

    Jan 2003 to July 2011

Study Arms (2)

Isoniazid preventive therapy

EXPERIMENTAL

HIV infected children living in a high TB prevalence area receive isonaizid prophylaxis daily, together with cotrimoxazole prohpylaxis either 3 times a week or daily.

Drug: IsoniazidDrug: Cotrimoxazole

Placebo

PLACEBO COMPARATOR

HIV infected children living in a high TB prevalence area receive placebo once daily

Drug: CotrimoxazoleOther: placebo

Interventions

isoniazidDRUG

isoniazid 10mg/kg orally, daily, for study period

Isoniazid preventive therapy
CotrimoxazoleDRUG

Cotrimoxazole given 3 times a week or daily, orally, for study period

Isoniazid preventive therapyPlacebo
placeboOTHER

Placebo tablet identicle in appearance to intervention: isoniazid table

Placebo

Eligibility Criteria

Age8 Weeks - 15 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • HIV-infected children
  • Resident in Cape Town
  • Informed consent obtainable
  • weight \> 2.5kg
  • Access to transport
  • HAART use for not less than 2 months but not more than 12 months with no significant demonstrated toxicity and good adherence

You may not qualify if:

  • Chronic diarrhoea
  • Current use of INH prophylaxis
  • Prior hypersensitivity to INH prior history of allergy to sulphur drugs
  • Prior history of allergy to sulphur drugs
  • Severe anaemia (haemoglobin less than 7 gm/dl)
  • Neutropenia (absoloute neutrophil count less than 400 cells)
  • Thrombocytopenia (platelet count \< 50 000/uL)
  • Non-reversible renal failure
  • Clinical hepatitis
  • Exposure to household TB contact, requiring INH prophylaxis

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Red Cross Childrens Hospital

Cape Town, Western Cape, 7700, South Africa

Location

Tygerberg Hospital

Cape Town, Western Cape, South Africa

Location

Related Publications (5)

  • Amlabu V, Mulligan C, Jele N, Evans A, Gray D, Zar HJ, McIlleron H, Smith P. Isoniazid/acetylisoniazid urine concentrations: markers of adherence to isoniazid preventive therapy in children. Int J Tuberc Lung Dis. 2014 May;18(5):528-30. doi: 10.5588/ijtld.13.0730.

    PMID: 24903787DERIVED

  • Gray DM, Workman LJ, Lombard CJ, Jennings T, Innes S, Grobbelaar CJ, Cotton MF, Zar HJ. Isoniazid preventive therapy in HIV-infected children on antiretroviral therapy: a pilot study. Int J Tuberc Lung Dis. 2014 Mar;18(3):322-7. doi: 10.5588/ijtld.13.0354.

    PMID: 24670570DERIVED

  • Frigati LJ, Kranzer K, Cotton MF, Schaaf HS, Lombard CJ, Zar HJ. The impact of isoniazid preventive therapy and antiretroviral therapy on tuberculosis in children infected with HIV in a high tuberculosis incidence setting. Thorax. 2011 Jun;66(6):496-501. doi: 10.1136/thx.2010.156752. Epub 2011 Apr 2.

    PMID: 21460373DERIVED

  • le Roux SM, Cotton MF, Golub JE, le Roux DM, Workman L, Zar HJ. Adherence to isoniazid prophylaxis among HIV-infected children: a randomized controlled trial comparing two dosing schedules. BMC Med. 2009 Nov 3;7:67. doi: 10.1186/1741-7015-7-67.

    PMID: 19886982DERIVED

  • Zar HJ, Cotton MF, Strauss S, Karpakis J, Hussey G, Schaaf HS, Rabie H, Lombard CJ. Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial. BMJ. 2007 Jan 20;334(7585):136. doi: 10.1136/bmj.39000.486400.55. Epub 2006 Nov 3.

    PMID: 17085459DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

IsoniazidTrimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Intervention Hierarchy (Ancestors)

HydrazinesOrganic ChemicalsIsonicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-RingSulfamethoxazoleBenzenesulfonamidesSulfonamidesAmidesSulfanilamidesAniline CompoundsAminesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsTrimethoprimPyrimidinesDrug CombinationsPharmaceutical Preparations

Study Officials

  • Heather J Zar, MD PHd

    University of Cape Town

    PRINCIPAL INVESTIGATOR

  • Mark Cotton, Md PhD

    University of Stellenbosch

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Purpose
PREVENTION
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

May 24, 2006

First Posted

May 26, 2006

Study Start

January 1, 2003

Primary Completion

November 15, 2011

Study Completion

November 15, 2011

Last Updated

April 22, 2019

Record last verified: 2019-04

Locations

ZA(2)