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

HIV Infections Clinical Trial

— CCS  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00674921
• Other study ID #: 009/ESR/NDA/DID-01/2008
• Status: Not yet recruiting
• Phase: Phase 4
• First received: May 6, 2008
• Last updated: June 4, 2008
• Start date: June 2008
• Est. completion date: June 2011

Study information

• Verified date: May 2008
• Source: MRC/UVRI Uganda Research Unit on Aids
• Contact: George Mukalazi Miiro, MSc, MBChB
• Phone: 256-414-320-272
• Email: george.miiro[@]mrcuganda.org
• Is FDA regulated: No
• Health authority: Uganda: National Council for Science and Technology
• Study type: Interventional

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1650
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 59 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections

Intervention

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
starch, magnesium stearate, sodium lauryl sulphate

Locations

Country	Name	City	State
Uganda	MRC/UVRI Uganda Research Unit on Aids	Entebbe

Sponsors (2)

Lead Sponsor	Collaborator
MRC/UVRI Uganda Research Unit on Aids	Medical Research Council

Country where clinical trial is conducted

Uganda, 

References & Publications (7)

Esposito S, Bojanin J, Porta A, Cesati L, Gualtieri L, Principi N. Discontinuation of secondary prophylaxis for Pneumocystis pneumonia in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy. Pediatr Infect Dis — View Citation

Furrer H, Egger M, Opravil M, Bernasconi E, Hirschel B, Battegay M, Telenti A, Vernazza PL, Rickenbach M, Flepp M, Malinverni R. Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1-infected adults treated with combinatio — View Citation

Ledergerber B, Mocroft A, Reiss P, Furrer H, Kirk O, Bickel M, Uberti-Foppa C, Pradier C, D'Arminio Monforte A, Schneider MM, Lundgren JD; Eight European Study Groups. Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in pati — View Citation

Lopez Bernaldo de Quiros JC, Miro JM, Peña JM, Podzamczer D, Alberdi JC, Martínez E, Cosin J, Claramonte X, Gonzalez J, Domingo P, Casado JL, Ribera E; Grupo de Estudio del SIDA 04/98. A randomized trial of the discontinuation of primary and secondary pro — View Citation

Mussini C, Pezzotti P, Antinori A, Borghi V, Monforte Ad, Govoni A, De Luca A, Ammassari A, Mongiardo N, Cerri MC, Bedini A, Beltrami C, Ursitti MA, Bini T, Cossarizza A, Esposito R; Changes in Opportunistic Prophylaxis (CIOP) Study Group. Discontinuation — View Citation

Weverling GJ, Mocroft A, Ledergerber B, Kirk O, Gonzáles-Lahoz J, d'Arminio Monforte A, Proenca R, Phillips AN, Lundgren JD, Reiss P. Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV- — View Citation

Zellweger C, Opravil M, Bernasconi E, Cavassini M, Bucher HC, Schiffer V, Wagels T, Flepp M, Rickenbach M, Furrer H; Swiss HIV Cohort Study. Long-term safety of discontinuation of secondary prophylaxis against Pneumocystis pneumonia: prospective multicent — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	all-cause morbidity such as pneumonia or malaria (presumptive and definitive diagnosis)		3 years	Yes
Secondary	sub-clinical laboratory abnormalities (such as neutropenia) and serious adverse events (such as death)		3 years	Yes