NCT00674921

Brief 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?

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,650

participants targeted

Target at P75+ for phase_4 hiv-infections

Timeline
Completed

Started Jun 2008

Typical duration for phase_4 hiv-infections

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 6, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 8, 2008

Completed
24 days until next milestone

Study Start

First participant enrolled

June 1, 2008

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2011

Completed
Last Updated

June 5, 2008

Status Verified

May 1, 2008

Enrollment Period

3 years

First QC Date

May 6, 2008

Last Update Submit

June 4, 2008

Conditions

HIV Infections

Keywords

Opportunistic InfectionsAIDSHIVTreatment Experienced

Outcome Measures

Primary Outcomes (1)

  • all-cause morbidity such as pneumonia or malaria (presumptive and definitive diagnosis)

    3 years

Secondary Outcomes (1)

  • sub-clinical laboratory abnormalities (such as neutropenia) and serious adverse events (such as death)

    3 years

Study Arms (4)

1

PLACEBO COMPARATOR

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

2

ACTIVE COMPARATOR

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

A

PLACEBO COMPARATOR

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

B

ACTIVE COMPARATOR

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

Interventions

cotrimoxazoleDRUG

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

2B
PlaceboDRUG

starch, magnesium stearate, sodium lauryl sulphate

1A

Eligibility Criteria

Age16 Years - 59 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

MRC/UVRI Uganda Research Unit on Aids

Entebbe, 256, Uganda

Location

Related Publications (7)

  • 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 multicentre study. AIDS. 2004 Oct 21;18(15):2047-53. doi: 10.1097/00002030-200410210-00009.

    PMID: 15577626RESULT

  • 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 of secondary prophylaxis for Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients: a randomized trial by the CIOP Study Group. Clin Infect Dis. 2003 Mar 1;36(5):645-51. doi: 10.1086/367659. Epub 2003 Feb 12.

    PMID: 12594647RESULT

  • 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 patients with HIV infection who have a response to antiretroviral therapy. Eight European Study Groups. N Engl J Med. 2001 Jan 18;344(3):168-74. doi: 10.1056/NEJM200101183440302.

    PMID: 11188837RESULT

  • 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 J. 2005 Dec;24(12):1117-20. doi: 10.1097/01.inf.0000190038.53813.d2.

    PMID: 16371882RESULT

  • Lopez Bernaldo de Quiros JC, Miro JM, Pena JM, Podzamczer D, Alberdi JC, Martinez 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 prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98. N Engl J Med. 2001 Jan 18;344(3):159-67. doi: 10.1056/NEJM200101183440301.

    PMID: 11172138RESULT

  • 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 combination antiretroviral therapy. Swiss HIV Cohort Study. N Engl J Med. 1999 Apr 29;340(17):1301-6. doi: 10.1056/NEJM199904293401701.

    PMID: 10219064RESULT

  • Weverling GJ, Mocroft A, Ledergerber B, Kirk O, Gonzales-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-1 infection. EuroSIDA Study Group. Lancet. 1999 Apr 17;353(9161):1293-8. doi: 10.1016/s0140-6736(99)03287-0.

    PMID: 10218526RESULT

MeSH Terms

Conditions

HIV InfectionsOpportunistic InfectionsAcquired Immunodeficiency Syndrome

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesSlow Virus Diseases

Intervention Hierarchy (Ancestors)

SulfamethoxazoleBenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsSulfanilamidesAniline CompoundsAminesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsTrimethoprimPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • George Miiro, MSc, MBChB

    MRC/UVRI Unit

    PRINCIPAL INVESTIGATOR

  • Heiner Grosskurth, PhD, MD

    MRC/UVRI Unit

    STUDY DIRECTOR

  • Paula Munderi, MRCP, MBChB

    MRC/UVRI Unit

    PRINCIPAL INVESTIGATOR

Central Study Contacts

George Mukalazi Miiro, MSc, MBChB

CONTACT

256-414-320-272george.miiro@mrcuganda.org

Heiner Grosskurth, PhD, MD

CONTACT

256-414-320-272heiner.grosskurth@mrcuganda.org

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
FACTORIAL
Sponsor Type
OTHER

Study Record Dates

First Submitted

May 6, 2008

First Posted

May 8, 2008

Study Start

June 1, 2008

Primary Completion

June 1, 2011

Study Completion

June 1, 2011

Last Updated

June 5, 2008

Record last verified: 2008-05

Locations

UG(1)