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

Plain English Summary

Not provided at time of registration

Study website

Type

Scientific

Contact name

Dr Paula Munderi

ORCID ID

Contact details

MCR/UVRI Uganda Research Unit on AIDS
Uganda Virus Research Institute
50 - 59 Nakiwogo Road
PO Box 49
Entebbe
-
Uganda
+256 (0)41 770 4152
paula.munderi@mrcuganda.org

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Protocol/serial number

Version 4.0 March 2010; G0902150

Scientific title

Safety of discontinuing co-trimoxaxole prophylaxis among human immunodeficiency virus (HIV) infected adults in Uganda: a randomised controlled trial

Acronym

COSTOP

Study hypothesis

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)

Study design

Randomised double-blind placebo-controlled non-inferiority trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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

Pharmaceutical study type(s)

Phase

Not Applicable

Drug/device/biological/vaccine name(s)

Co-trimoxazole

Primary outcome measure

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 measures

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

Overall study start date

01/09/2010

Overall study end date

30/03/2014

Reason abandoned (if study stopped)

Participant 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

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Upper age limit

59 Years

Sex

Both

Target number of participants

2000

Participant 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

Recruitment start date

01/09/2010

Recruitment end date

30/03/2014

Countries of recruitment

Uganda

Study participating centre

MCR/UVRI Uganda Research Unit on AIDS
Entebbe
-
Uganda

Organisation

MRC/UVRI Uganda Research Unit on AIDS (Uganda)

Sponsor details

Uganda Virus Research Institute
50 - 59 Nakiwogo Road
PO Box 49
Entebbe
-
Uganda
+256 (0)41 770 4000
mrc@mrcuganda.org

Sponsor type

Research organisation

Website

http://www.mrcuganda.org/

ROR

https://ror.org/04509n826

Funder type

Research council

Funder name

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

Alternative name(s)

UK Medical Research Council, MRC

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Individual participant data (IPD) sharing plan

IPD sharing plan summary

Not provided at time of registration

Study outputs