Safety of discontinuing co-trimoxazole prophylaxis among Ugandan adults on antiretroviral therapy (ART)
| ISRCTN | ISRCTN44723643 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN44723643 |
| Secondary identifying numbers | Version 4.0 March 2010; 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
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 |
|---|---|
| paula.munderi@mrcuganda.org |
Study information
| 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 |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 |
| 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 |
| Completion date | 30/03/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 59 Years |
| Sex | Both |
| Target number of participants | 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
-
Uganda
Sponsor information
MRC/UVRI Uganda Research Unit on AIDS (Uganda)
Research organisation
Research organisation
Uganda Virus Research Institute
50 - 59 Nakiwogo Road
PO Box 49
Entebbe
-
Uganda
| Phone | +256 (0)41 770 4000 |
|---|---|
| mrc@mrcuganda.org | |
| Website | http://www.mrcuganda.org/ |
"ROR" |
https://ror.org/04509n826 |
Funders
Funder type
Research council
Medical Research Council (MRC) (UK) (ref: G0902150)
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 |
Editorial Notes
17/02/2021: Publication reference added.
18/12/2017: publication references added.
