Safety of discontinuing co-trimoxazole prophylaxis among Ugandan adults on antiretroviral therapy (ART)

• Register: ISRCTN
• Last refreshed on: 1 March 2021
• Main ID: ISRCTN44723643
• Date of registration: 27/08/2010
• Prospective Registration: Yes
• Primary sponsor: MRC/UVRI Uganda Research Unit on AIDS (Uganda)
• Public title: Safety of discontinuing co-trimoxazole prophylaxis among Ugandan adults on antiretroviral therapy (ART)
• Scientific title: Safety of discontinuing co-trimoxaxole prophylaxis among human immunodeficiency virus (HIV) infected adults in Uganda: a randomised controlled trial
• Date of first enrolment: 01/09/2010
• Target sample size: 2000
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN44723643
• Study type: Interventional
• Study design: Randomised double-blind placebo-controlled non-inferiority trial (Treatment)
• Phase: Not Applicable

Countries of recruitment

Uganda

Contacts

• Name: Paula Munderi

Key inclusion & exclusion criteria

Inclusion criteria:
1. Human immunodeficiency virus (HIV) infected patient taking co-trimoxazole for at least 6 months
2. Aged 18 - 59 years, either sex
3. Documented intake of ART for at least 6 months
4. Clinically asymptomatic
5. Two CD4 counts (not more than 6 months apart) greater than or equal to 250 cells/mm3, the most recent no more than 4 weeks prior to enrolment
6. Able to attend 3-monthly study clinics for appointments and in event of intercurrent illness

Exclusion criteria:
1. Acute illness (opportunistic infection or other co- morbidity). Patients will be considered for inclusion into the trial after resolution of the illness.
2. First trimester pregnancy. Pregnant women who reach their second trimester of pregnancy could then be re-evaluated for inclusion into the trial.
3. Known hypersensitivity to co-trimoxazole


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic human immunodeficiency virus (HIV) infection
Infections and Infestations
Human immunodeficiency virus

Intervention(s)

Patients who fulfil the inclusion criteria and who do not meet exclusion criteria will be recruited sequentially and will be randomised 1:1 to the experimental or control group:
1. Experimental group: Patients with CD4 count 250 or more cells/mm3 discontinue prophylaxis with co-trimoxazole (CTX), receive CTX placebo and continue taking antiretroviral therapy.
2. Standard/control group: Patients with CD4 count 250 or more cells/mm3 continue prophylaxis with co-trimoxazole (CTX), receive active CTX and continue taking antiretroviral therapy.

Primary Outcome(s)

1. Efficacy: time to the occurrence of the first clinical event (pre-defined CTX-preventable opportunistic clinical event or death)
2. Safety: time to the occurrence of the first grade 3 or 4 haematological adverse event

Recorded at first occurrence during the trial and assessed at the end of the trial.

Secondary Outcome(s)

1. Incidence of all CTX preventable events, recorded at time of occurrence
2. All cause mortality, recorded at time of occurrence
3. Incidence of all clinical events and related events requiring hospitalisation, recorded at time of occurrence
4. Incidence of all confirmed malaria episodes* asymptomatic and symptomatic, recorded at time of occurrence
5. Severity and outcome of all confirmed malaria episodes* asymptomatic and symptomatic, recorded at time of occurrence
6. Incidence of grade 3 or grade 4 adverse events, recorded at time of occurrence
7. Mean change in CD4 count after 12 months on the trial
8. Mean change in haematologic indices after 12 months on the trial
9. Serious adverse events (SAEs)-according to International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) definitions, recorded at time of occurrence
10. Adherence to use of ART, trial drug and insecticide-treated mosquito nets, evaluated at end of trial

* confirmed by positive parasitaemia on a blood slide

Secondary ID(s)

Version 4.0 March 2010; G0902150

Source(s) of Monetary Support

Medical Research Council (MRC) (UK) (ref: G0902150)

Ethics review

Status:
Approval date:
Contact:

Uganda Virus Research Institute Science and Ethics Committee approved on the 17th June 2010 (ref: GC/127/10/07)

Results

• Results available: Yes
• Date Completed: 30/03/2014