Cotrimoxazole Prophylaxis Cessation Study Among Stabilized HIV-Infected Adult Patients on HAART in Entebbe, Uganda
Information source: MRC/UVRI Uganda Research Unit on Aids
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: cotrimoxazole (Drug); Placebo (Drug)
Phase: Phase 4
Status: Not yet recruiting
Sponsored by: MRC/UVRI Uganda Research Unit on Aids Official(s) and/or principal investigator(s): George Miiro, MSc, MBChB, Principal Investigator, Affiliation: MRC/UVRI Unit Heiner Grosskurth, PhD, MD, Study Director, Affiliation: MRC/UVRI Unit Paula Munderi, MRCP, MBChB, Principal Investigator, Affiliation: MRC/UVRI Unit
Overall contact: George Mukalazi Miiro, MSc, MBChB, Phone: 256-414-320-272, Email: george.miiro@mrcuganda.org
Summary
According to the national guidelines in Uganda and to the World Health Organization
guidelines, HIV-infected patients should receive cotrimoxazole prophylaxis indefinitely.
There are, however, concerns regarding the indefinite application of cotrimoxazole
prophylaxis among patients immunologically stabilized on HAART (e. g. high pill burden,
drug-drug interactions, toxicity and poor adherence because of treatment fatigue). To date
no empirical evidence is available regarding the safety and optimal timing for the cessation
of cotrimoxazole prophylaxis among HAART patients who successfully restored immunological
competence.
Research question: Does morbidity significantly differ between continuation (orthodox) and
cessation (experimental) of cotrimoxazole prophylaxis among immuno-competent patients stable
HAART in the resource-limited setting of Uganda?
Clinical Details
Official title: Cotrimoxazole Prophylaxis Cessation Study Among Stabilized HIV-Infected Adult Patients on HAART in Entebbe, Uganda
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: all-cause morbidity such as pneumonia or malaria (presumptive and definitive diagnosis)
Secondary outcome: sub-clinical laboratory abnormalities (such as neutropenia) and serious adverse events (such as death)
Detailed description:
Randomized double-blind placebo controlled equivalence trial to be conducted among
consenting clinically healthy patients on HAART with 2 or more CD4 counts of 200 cells/ul or
more for at least 3 months. The study will enable comparison of effects of randomized
cessation of cotrimoxazole prophylaxis at 2 CD4-guided thresholds (200 Vs 350 cells/ul).
Rationale for inclusion of the placebo-controlled design
- The double-blind placebo controlled approach is feasible and ethically justified in
this equipoise situation to allow for concealment of allocated intervention among
investigators and patients and avoids accidental unblinding of investigators to the
allocated interventions by trial patients.
- Maintenance of continued cotrimoxazole prophylaxis among patients randomized to this
intervention will be easier if there is no awareness that those patients randomized to
cessation of prophylaxis have a relative advantage of reduced pill burden.
- It would be very difficult to maintain cessation of cotrimoxazole prophylaxis among
patients randomized to do so in our setting where cotrimoxazole is readily and cheaply
available in drug shops, drug stores and pharmacies.
First randomisation
Patients who have been on HAART for at least 3 months and who have a confirmed CD4 count
between 200 and 349 cells/ul will be randomized to continue prophylaxis with active
cotrimoxazole or to cease prophylaxis with active cotrimoxazole but continue with ingestion
of the placebo cotrimoxazole daily.
Second randomization
Patients who achieve a confirmed CD4 count of 350 cells/ul or more while on HAART will be
randomized to continue prophylaxis with active cotrimoxazole or to cease prophylaxis with
active cotrimoxazole but continue with ingestion of placebo cotrimoxazole daily. Some
patients will have participated already in 1st randomization but others will be entering the
trial at this stage for the first time.
Rationale for 4 trial arms
In order to assess the separate effects of cessation of cotrimoxazole prophylaxis in trial
patients at the 2 randomization stages above, those continuing with prophylaxis will be
compared with those ceasing prophylaxis, necessitating 2 arms at each stage.
Eligibility
Minimum age: 16 Years.
Maximum age: 59 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Consenting HIV-infected patient aged 16 years or older,
- Resident within 40 kms of study clinics
- Regularly attending clinics
- Documented HAART intake for at least 3 months
- Clinically healthy and stable
- Confirmed CD4 count of 200 cells/ul more.
Exclusion Criteria:
- Acutely ill patients with opportunistic or other infections
- Patients already enrolled in other HAART trials (e. g DART trial)
- First trimester pregnancy at enrolment
- Clinical and immunological evidence of HAART treatment failure
- Unable to attend study clinics regularly
- Hypersensitivity to cotrimoxazole
Locations and Contacts
George Mukalazi Miiro, MSc, MBChB, Phone: 256-414-320-272, Email: george.miiro@mrcuganda.org
MRC/UVRI Uganda Research Unit on Aids, Entebbe 256, Uganda
Additional Information
Starting date: June 2008
Last updated: June 4, 2008
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