Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on ART in Blantyre, Malawi (TSCQ)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by University of Maryland
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Miriam Laufer, University of Maryland
ClinicalTrials.gov Identifier:
NCT01650558
First received: July 6, 2012
Last updated: December 10, 2012
Last verified: December 2012

July 6, 2012
December 10, 2012
November 2012
April 2016   (final data collection date for primary outcome measure)
Severe events [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
Incidence of severe events (composite of death and WHO stage 3 and 4 illness)
Serious Adverse Events that are deemed probably or definitively associated with the study interventions and the total SAEs in each group. [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: Yes ]
The primary endpoint events (deaths, World Health Organization stage 3 and 4 events) as well as ≥Grade 3 adverse events and the rates of discontinuation of TS or CQ prophylaxis will thus necessarily be included in the safety review.
Complete list of historical versions of study NCT01650558 on ClinicalTrials.gov Archive Site
  • HIV viral load [ Time Frame: Every 6 months for 2-3.5 years ] [ Designated as safety issue: No ]
    Incidence of detectable viral load (>400 copies/ml)
  • CD4 cell count [ Time Frame: Every 6 months for 2-3.5 years ] [ Designated as safety issue: No ]
    CD4 cell counts compared among those on prophylaxis with TS or CQ versus no prophylaxis
  • WHO HIV stage 2, 3, 4 illness [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
    Incidence of any WHO HIV stage 2, 3, or 4 illness
  • Bacterial infections and malaria [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
    Incidence of bacterial infections and malaria
  • Adverse events greater than or equal to Grade 3 that are related to the study product [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: Yes ]
    Occurrence of adverse events that are greater than or equal to Grade 3 that require discontinuation of TS or CQ prophylaxis
Not Provided
  • Bacterial or malaria infection with CQ or TS resistant organism [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
    Occurrence of bacterial or malaria infection with CQ or TS resistant organism
  • Clinical and parasitological response to antimalarial therapy [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]
    Clinical and parasitological response to antimalarial therapy in cases of uncomplicated malaria
Not Provided
 
Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on ART in Blantyre, Malawi
Randomized, Open-label Controlled Trial of Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on Anti-retroviral Therapy in Blantyre, Malawi

The purpose of this study is to determine if there is a benefit to taking trimethoprim-sulfamethoxazole (TS) as prophylaxis among HIV positive adults who have viral load suppression and a good clinical response on anti-retroviral therapy (ART). If there is a benefit, then is it due to antimalarial or antibacterial properties.

The investigators hypothesize that there will be a long-term benefit on survival and disease control in the context of prophylaxis and that the benefit will largely be attributed to prevention of malaria. The main study hypothesis is that 1)TS and chloroquine (CQ) will decrease the rates of morbidity and mortality among adults after 6 or more months of ART and 2) CQ prophylaxis will be associated with more prolonged viral suppression and higher CD4 cell counts than TS prophylaxis or no prophylaxis.

This is a randomized, controlled, open-label, phase III trial of standard of care TS prophylaxis and CQ prophylaxis compared to no prophylaxis in adults receiving ART. Adults who have been receiving ART for at least six months with a good clinical response and provide informed consent and fulfill the eligibility criteria will be randomized to one of three arms: (1) to continue standard of care trimethoprim-sulfamethoxazole (TS) prophylaxis, (2) discontinue standard of care TS prophylaxis and begin weekly CQ prophylaxis or (3) discontinue standard of care TS prophylaxis. Participants will be asked to return to the research clinic every four weeks and any time they are ill to facilitate both active and passive follow-up of the study endpoints. Participation will last for 24 to approximately 42 months. Participants who develop a WHO clinical stage 3 or 4 illness (see Appendix A for a complete listing), experience a sustained decline in their CD4 count below 200 cells/mm3, or who experience ART failure will be placed on standard of care TS prophylaxis. Those with confirmed ART failure will be evaluated for second-line therapy according to the Malawi Ministry of Health guidelines.

The study population will include 900 Malawian adults aged 18 years or older living with HIV in or near Blantyre, Malawi, Central Africa who have been receiving antiretroviral therapy for at least 6 months with good clinical response to ART, have an undetectable HIV viral load and a CD4 count >250/mm3. Participants must intend to stay in Blantyre for the entire study period.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Prevention
HIV
  • Drug: Standard of Care prophylaxis
    Daily trimethoprim sulfamethoxazole
    Other Names:
    • Bactrim
    • Co-trimoxazole
  • Drug: Chloroquine (CQ) prophylaxis
    Discontinue standard of care and start weekly CQ.
    Other Name: Aralen
  • Active Comparator: Standard of Care Prophylaxis (TS)
    Standard of care prophylaxis with daily trimethoprim sulfamethoxazole (TS).
    Intervention: Drug: Standard of Care prophylaxis
  • Experimental: Chloroquine (CQ) prophylaxis
    Discontinuation of standard of care TS prophylaxis and starting weekly chloroquine prophylaxis
    Intervention: Drug: Chloroquine (CQ) prophylaxis
  • No Intervention: Discontinuation of standard of care
    Control arm - Discontinuation of standard of care trimethoprim sulfamethoxazole.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
900
April 2016
April 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age 18 years or older
  • Documented HIV-1 infection
  • Initiation of ART through a government-sponsored ART program at least six months prior
  • Undetectable HIV viral load (< 400 copies/mL)
  • CD4 count > 250/mm3
  • TS prophylaxis prescribed for at least the previous 2 months
  • Intention to remain in the study area until the end of the study period
  • Informed consent from participant
  • Female study volunteers of reproductive potential must have a negative serum urine pregnancy test performed within 20 days before randomization.
  • Female study volunteers of reproductive potential who participate in sexual activity that could lead to pregnancy must use contraception (male or female condoms, diaphragm or cervical cap with spermicide, intrauterine device, or hormone-based contraceptive) while receiving their assigned study drug and for one month after stopping the medications.

Exclusion Criteria:

  • Severe acute illness (defined as requiring hospitalization at the time of screening or other conditions such as laboratory abnormalities as determined by the investigators)
  • Chronic treatment (requiring therapy for > 14 days) or secondary prophylaxis (for toxoplasmosis, Pneumocystis pneumonia, or tuberculosis for example) with any drug with antimalarial or antibacterial activity
  • History of hypersensitivity to antifolate drugs or CQ
  • Laboratory exclusion criteria
  • Hemoglobin < 8.0 gm/dL
  • Platelet count < 50,000/mm3
  • Absolute granulocyte count < 500/mm3
  • Serum alanine aminotransferase (ALT) concentration > 210 U/L for men, >160 U/L for women
  • Serum creatinine concentration > 3.3mg/dl (291.7µmol/L) for men, and > 2.7mg/dl (238.7µmol/L) for women)
  • History of visual field or retinal changes
  • History of preexisting auditory damage
  • History of porphyria
  • History of psoriasis
  • History of liver disease
  • History of seizure disorder
  • History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • History of ECG and cardiac conduction abnormality or cardiomyopathy
  • History of myopathy
Both
18 Years and older
No
Malawi
 
NCT01650558
HP-00043360; DAIDS ES-10822, U01AI089342-01A1
Yes
Miriam Laufer, University of Maryland
University of Maryland
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: Miriam K Laufer, MD, MPH University of Maryland, Baltimore County
University of Maryland
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP