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Clinical Trials

MainTitle

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

This study is ongoing, but not recruiting participants.
Sponsor
University of Maryland

Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by (Responsible Party)
Miriam Laufer, University of Maryland

ClinicalTrials.gov Identifier
NCT01650558

First received: July 6, 2012
Last updated: September 18, 2017
Last Verified: September 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention
HIV

Drug : Standard of Care prophylaxis
Drug : Chloroquine (CQ) prophylaxis

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Randomized, Open-label Controlled Trial of Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on Anti-retroviral Therapy in Malawi

Further study details as provided by Miriam Laufer, University of Maryland:

Primary Outcome Measures

  • Severe events [ Time Frame: 32-66 months ]
    Incidence of severe events (composite of death and WHO stage 3 and 4 illness)
Secondary Outcome Measures:
  • 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
Other Outcome Measures:
  • 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

Estimated Enrollment: 1500
Study Start Date: November 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: Standard of Care Prophylaxis (TS)
Standard of care prophylaxis with daily trimethoprim sulfamethoxazole (TS).
Drug: Standard of Care prophylaxis

Daily trimethoprim sulfamethoxazole

Other Name:
  • Bactrim
  • Co-trimoxazole

Experimental: Chloroquine (CQ) prophylaxis
Discontinuation of standard of care TS prophylaxis and starting weekly chloroquine prophylaxis
Drug: Chloroquine (CQ) prophylaxis

Discontinue standard of care and start weekly CQ.

Other Name: Aralen
No Intervention: Discontinuation of standard of care
Control arm - Discontinuation of standard of care trimethoprim sulfamethoxazole.

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01650558

Locations

Malawi
Blantyre Malaria Project Research Clinic
Blantyre, Malawi
Tisungane Clinic
Zomba, Malawi

Sponsors and Collaborators

University of Maryland
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator: Miriam K Laufer, MD, MPH University of Maryland
More Information

More Information


Responsible Party: Miriam Laufer, Associate Professor of Pediatrics, University of Maryland  
ClinicalTrials.gov Identifier: NCT01650558   History of Changes  
Other Study ID Numbers: HP-00043360; DAIDS ES-10822  
  U01AI089342-01A1  
Study First Received: July 6, 2012  
Last Updated: September 18, 2017  

Keywords provided by Miriam Laufer, University of Maryland:

Malaria
HIV
Prophylaxis
Antiretroviral therapy

Additional relevant MeSH terms:
Chloroquine
Chloroquine diphosphate
Trimethoprim
Trimethoprim, Sulfamethoxazole Drug Combination
Sulfamethoxazole

ClinicalTrials.gov processed this data on October 16, 2017
This information is provided by ClinicalTrials.gov.