Cotrimoxazole Prophylaxis Cessation Study Among Stabilized HIV-Infected Adult Patients on HAART in Entebbe, Uganda (CCS)

June 4, 2008 updated by: MRC/UVRI and LSHTM Uganda Research Unit

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?

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

1650

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Uganda
      • Entebbe, Uganda, 256
        • MRC/UVRI Uganda Research Unit on AIDS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 59 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 1
It will comprise patients randomized to receive the placebo (stop cotrimoxazole prophylaxis) at CD4 counts of 200 or more but less than 350 cells/ul as they continue with HAART. Patients will be followed until they achieve a CD4 count of 350 cells/ul.
Drug: Placebo
starch, magnesium stearate, sodium lauryl sulphate
Active Comparator: 2
It will comprise patients randomized to continue with cotrimoxazole prophylaxis and HAART at CD4 counts of 200 or more but less than 350 cells/ul. These patients will be followed until they achieve a CD4 count of 350 cells/ul and above, at which point they will be considered for the second randomization.
Drug: cotrimoxazole
cotrimoxazole 800/160 mg once daily as indicated by the start and end times of the specified arms for continued prevention of HIV-related infections
Placebo Comparator: A
This arm will comprise patients who have achieved a CD4 count of 350 or more cells/ul either at the beginning of the study or once they have reached this threshold at the end of follow up in arms 1 and 2. They (including those previously in Arm 1) will receive the placebo (stop cotrimoxazole prophylaxis) after the second randomization but continue with HAART.
Drug: Placebo
starch, magnesium stearate, sodium lauryl sulphate
Active Comparator: B
It will comprise patients randomized to continue or start with cotrimoxazole prophylaxis and HAART at CD4 of 350 or more cells/ul after second randomization. Some of them will have used cotrimoxazole prophylaxis whilst they were in arm 2 and others in arm 1 will restart cotrimoxazole prophylaxis at this stage.
Drug: cotrimoxazole
cotrimoxazole 800/160 mg once daily as indicated by the start and end times of the specified arms for continued prevention of HIV-related infections

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
all-cause morbidity such as pneumonia or malaria (presumptive and definitive diagnosis)
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
sub-clinical laboratory abnormalities (such as neutropenia) and serious adverse events (such as death)
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MRC/UVRI and LSHTM Uganda Research Unit

Collaborators

Medical Research Council

Investigators

  • Principal Investigator: George Miiro, MSc, MBChB, MRC/UVRI Unit
  • Study Director: Heiner Grosskurth, PhD, MD, MRC/UVRI Unit
  • Principal Investigator: Paula Munderi, MRCP, MBChB, MRC/UVRI Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Anticipated)

June 1, 2011

Study Completion (Anticipated)

June 1, 2011

Study Registration Dates

First Submitted

May 6, 2008

First Submitted That Met QC Criteria

May 6, 2008

First Posted (Estimate)

May 8, 2008

Study Record Updates

Last Update Posted (Estimate)

June 5, 2008

Last Update Submitted That Met QC Criteria

June 4, 2008

Last Verified

May 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 009/ESR/NDA/DID-01/2008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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