Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01650558
Recruitment Status : Completed
First Posted : July 26, 2012
Last Update Posted : March 29, 2019
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Miriam Laufer, University of Maryland, College Park

Tracking Information
First Submitted Date  ICMJE July 6, 2012
First Posted Date  ICMJE July 26, 2012
Last Update Posted Date March 29, 2019
Study Start Date  ICMJE November 2012
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2015)
Severe events [ Time Frame: 32-66 months ]
Incidence of severe events (composite of death and WHO stage 3 and 4 illness)
Original Primary Outcome Measures  ICMJE
 (submitted: July 23, 2012)
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 ]
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.
Change History Complete list of historical versions of study NCT01650558 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2015)
  • HIV viral load [ Time Frame: Every 6 months for 32-66 months ]
    Incidence of detectable viral load (>400 copies/ml)
  • CD4 cell count [ Time Frame: Every 6 months for 32-66 months ]
    CD4 cell counts compared among those on prophylaxis with TS or CQ versus no prophylaxis
  • WHO HIV stage 2, 3, 4 illness [ Time Frame: 32-66 months ]
    Incidence of any WHO HIV stage 2, 3, or 4 illness
  • Bacterial infections and malaria [ Time Frame: 32-66 months ]
    Incidence of bacterial infections and malaria
  • Adverse events greater than or equal to Grade 3 that are related to the study product [ Time Frame: 32-66 months ]
    Occurrence of adverse events that are greater than or equal to Grade 3 that require discontinuation of TS or CQ prophylaxis
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: June 15, 2015)
  • Bacterial or malaria infection with CQ or TS resistant organism [ Time Frame: 32-66 months ]
    Occurrence of bacterial or malaria infection with CQ or TS resistant organism
  • Clinical and parasitological response to antimalarial therapy [ Time Frame: 32-66 months ]
    Clinical and parasitological response to antimalarial therapy in cases of uncomplicated malaria
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on ART in Malawi
Official Title  ICMJE Randomized, Open-label Controlled Trial of Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on Anti-retroviral Therapy in Malawi
Brief Summary

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.

Detailed Description

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 for the first 24 weeks then every 12 weeks thereafter, and any time they are ill to facilitate both active and passive follow-up of the study endpoints. Participation will last for 32 to approximately 66 months. Participants who develop a WHO clinical stage 3 or 4 illness, 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 up to 1500 Malawian adults aged 18 years or older living with HIV in or near Blantyre or Zomba, 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE HIV
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
Publications * Laurens MB, Mungwira RG, Nyirenda OM, Divala TH, Kanjala M, Muwalo F, Mkandawire FA, Tsirizani L, Nyangulu W, Mwinjiwa E, Taylor TE, Mallewa J, Blackwelder WC, Plowe CV, Laufer MK, van Oosterhout JJ. TSCQ study: a randomized, controlled, open-label trial of daily trimethoprim-sulfamethoxazole or weekly chloroquine among adults on antiretroviral therapy in Malawi: study protocol for a randomized controlled trial. Trials. 2016 Jul 18;17(1):322. doi: 10.1186/s13063-016-1392-3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 27, 2019)
1499
Original Estimated Enrollment  ICMJE
 (submitted: July 23, 2012)
900
Actual Study Completion Date  ICMJE July 31, 2018
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Malawi
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01650558
Other Study ID Numbers  ICMJE HP-00043360; DAIDS ES-10822
U01AI089342-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Miriam Laufer, University of Maryland, College Park
Study Sponsor  ICMJE University of Maryland, College Park
Collaborators  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Investigators  ICMJE
Principal Investigator: Miriam K Laufer, MD, MPH University of Maryland, College Park
PRS Account University of Maryland, Baltimore
Verification Date March 2019

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