Drug Combinations of Atovaquone-Proguanil (AP) With ACT

• Status: Recruiting
• Trial end date: 2022-12-30
• Target enrollment: 0
• Participant gender: All

Summary

Investigators are conducting this study due to recent reports of many of existing malaria drugs becoming less effective for treatment of malaria. The drugs may not always kill all the parasites, therefore not all patients with malaria are being cured. The main objective of the study is to find out which malaria drugs and what drug combinations are still effective in Cambodia, an area of multi-drug resistance where 4-5 artemisinin-based combination therapies have shown inadequate response, below that established by the World Health Organization (WHO). New drug combinations (taking more than one drug for malaria at the same time), as long as well tolerated, can provide cure in patients that harbor parasites not responsive to standard first-line medications. Human genetic testing will be done to identify patients who may have suboptimal response to treatments and to study the differences in human gene expression to explain why some persons are at higher risk of complications during treatment. Markers of drug resistance to commonly used antimalarial drugs will also be evaluated and shared with national malaria program (CNM) to better guide future malaria treatment decisions in Cambodia.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Armed Forces Research Institute of Medical Sciences, Thailand
• Collaborators: National Center for Parasitology, Entomology and Malaria Control; National Center for Parasitology, Entomology, and Malaria Control (CNM); Naval Medical Research Unit-2 (NAMRU-2)
• Treatments: Artemisinins; Artesunate; Atovaquone; Atovaquone, proguanil drug combination; Mefloquine; Proguanil; Pyronaridine

Criteria

Inclusion Criteria:

• Understands Khmer spoken language

• Male or female (18 to 70 years old)

• Microscopic confirmation of asexual stages of Pf or mixed infection with Pf, with baseline asexual parasite densities between 100/µL to 200,000/µL

• Able to take oral medications

• Hemoglobin on day of enrollment ≥9.0 g/dL

• Agree to follow-up for the anticipated study duration, including a minimum of 3 nights at the medical treatment facility (inpatient hospitalization) and weekly follow-up visits for at least 6 weeks

• If the volunteer is on active duty in the military, the volunteer has written permission from their supervisor or states to have been authorized by his/her supervisor or the local commander to participate; and allow study staff to contact their supervisor to confirm this information

Exclusion Criteria:

• Known allergic reaction to any of the study drugs or history of severe intolerance to any of the antimalarials used in this study.

• Pregnant or lactating females and females of childbearing potential who do not agree to use an acceptable form of contraception during the study period and for 6 weeks following the last dose of the study drug.

• Symptoms of severe vomiting (inability to tolerate oral fluids or oral medications during the previous 8 hours or vomiting >3 times in the last 24 hrs).

• Diagnosis of severe malaria

• Abnormal liver function tests i.e AST or ALT or total bilirubin > 1.5 upper limit of normal (ULN) with nausea AND right upper quadrant abdominal pain OR jaundice on exam

• Isolated AST or ALT or Total Bilirubin >2x ULN

• Known significant cardiovascular, liver or renal abnormality or any other clinically significant illness, which in the opinion of the investigator would place the volunteer at significantly higher risk

• Treatment for malaria within the last 4 weeks

• Unable to provide informed consent

• Judged by the investigator to be otherwise unsuitable for study participation (to include, but not limited to, taking other medications that are known to cause serious drug-drug interactions with the study drugs, as determined by the study physician, or having suspected medical condition or taking other drugs that may affect test results interpretation or put the volunteer at much higher risk)