Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on ART in Blantyre, Malawi (TSCQ)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 Endpoint Classification: Safety Study Intervention Model: Factorial Assignment Masking: 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 Blantyre, Malawi |
- 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)
- 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
- 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
| Estimated Enrollment: | 900 |
| Study Start Date: | November 2012 |
| Estimated Study Completion Date: | April 2016 |
| Estimated Primary Completion Date: | April 2016 (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 Names:
|
|
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 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Malawi | |
| Blantyre Malaria Project Research Clinic | Recruiting |
| Blantyre, Malawi | |
| Contact: Randy Mungwira, MD +265-1-875-021 rgmungwira@gmail.com | |
| Contact: Jane Mallewa, MD +265 1-874-628 janemallewa@yahoo.com | |
| Sub-Investigator: Joep JG van Oosterhout, MD | |
| Sub-Investigator: Matthew B Laurens, MD, MPH | |
| Sub-Investigator: Terrie E Taylor, DO | |
| Principal Investigator: | Miriam K Laufer, MD, MPH | University of Maryland, Baltimore County |
More Information
No publications provided
| 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: | December 10, 2012 |
| Health Authority: | United States: Institutional Review Board United States: Data and Safety Monitoring Board Malawi: College of Medicine Research and Ethics Committee |
Keywords provided by University of Maryland:
|
Malaria HIV Prophylaxis Antiretroviral therapy |
Additional relevant MeSH terms:
|
Chloroquine Chloroquine diphosphate Trimethoprim Trimethoprim-Sulfamethoxazole Combination Sulfamethoxazole Amebicides Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antimalarials Antirheumatic Agents Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic |
Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Filaricides Antinematodal Agents Anthelmintics Central Nervous System Agents Anti-Infective Agents, Urinary Renal Agents Folic Acid Antagonists Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 21, 2013