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

ISRCTN	ISRCTN44723643
DOI	https://doi.org/10.1186/ISRCTN44723643
Protocol serial number	Version 4.0 March 2010; G0902150
Sponsor	MRC/UVRI Uganda Research Unit on AIDS (Uganda)
Funder	Medical Research Council (MRC) (UK) (ref: G0902150)

Submission date: 28/06/2010
Registration date: 27/08/2010
Last edited: 17/02/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Paula Munderi
Scientific

MCR/UVRI Uganda Research Unit on AIDS
Uganda Virus Research Institute
50 - 59 Nakiwogo Road
PO Box 49
Entebbe
-
Uganda

Phone	+256 (0)41 770 4152
Email	paula.munderi@mrcuganda.org

Study information

Primary study design	Interventional
Study design	Randomised double-blind placebo-controlled non-inferiority trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Safety of discontinuing co-trimoxaxole prophylaxis among human immunodeficiency virus (HIV) infected adults in Uganda: a randomised controlled trial
Study acronym	COSTOP
Study objectives	Stopping concurrent prophylactic treatment with co-trimoxazole in adult Ugandan patients on antiretroviral therapy, will not lead to an excess of clinical events (predefined co-trimoxazole preventable clinical events) or death, but will lead to a significant reduction in the incidence of grade 3 or 4 haematological adverse events of antiretroviral therapy (ART).
Ethics approval(s)	Uganda Virus Research Institute Science and Ethics Committee approved on the 17th June 2010 (ref: GC/127/10/07)
Health condition(s) or problem(s) studied	Chronic human immunodeficiency virus (HIV) infection
Intervention	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.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Co-trimoxazole
Primary outcome measure(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.
Key secondary outcome measure(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
Completion date	30/03/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	59 Years
Sex	All
Target sample size at registration	2000
Key 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
Key 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
Date of first enrolment	01/09/2010
Date of final enrolment	30/03/2014

Locations

Countries of recruitment

Uganda

Study participating centre

MCR/UVRI Uganda Research Unit on AIDS

Entebbe
-
Uganda

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	Incidence of malari results	20/02/2016		Yes	No
Results article	Longitudinal effect results	15/07/2016		Yes	No
Results article	Effect of antiretroviral therapy results	20/02/2017		Yes	No
Results article	immunology substudy results	06/07/2020	17/02/2021	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

17/02/2021: Publication reference added.
18/12/2017: publication references added.