Antimalarial Drug Resistance With Assessment of Transmission Blocking Activity

David Saunders

Status: Suspended

Conditions: Uncomplicated Plasmodium Falciparum Malaria

Treatments: Drug: DHA-piperaquine and Primaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT01849640

HRPO Log Number A-17145 (Other Identifier)

WRAIR#1877

Details and patient eligibility

About

This is a two-arm, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a three-day course of Dihydroartemisinin-Piperaquine (DP) with or without single-dose primaquine in patients with uncomplicated Plasmodium falciparum malaria. On the last day of DP therapy, volunteers will be randomized to receive either a single 45 mg dose of primaquine (PQ) or DP treatment only (no primaquine).

Full description

Volunteers with uncomplicated malaria in Cambodia will be enrolled to current standard of care therapy with DHA-piperaquine to monitor therapeutic efficacy and measure resistance. The cardiac safety of piperaquine will be monitored with electrocardiograms during the treatment period. Resistance to DP and DP-PQ will be assessed by a combination of clinical, pharmacologic, and parasitologic parameters including genomic signatures of selection during careful weekly follow-up visits for 42 days. Volunteers will be randomized on day 3 to either a single 45mg dose of primaquine or no sexual stage therapy to evaluate effects of primaquine on the sexual stages of malaria (gametocytes) and potential transmissibility of infection to Anopheles mosquitoes as compared to those not treated with primaquine.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Volunteer with uncomplicated P. falciparum malaria (volunteers with mixed P. falciparum and P. vivax infections may be enrolled), 18-65 years of age
2. Baseline asexual parasite density between 1,000-200,000 parasites/uL
3. Able to provide informed consent
4. Available and agree to follow-up for anticipated study duration including 3 day treatment course at the MTF and weekly follow-up for the 42-day period
5. Authorized by local commander to participate if active duty military

Exclusion criteria

1. Allergic reaction or contraindication to DHA, piperaquine or primaquine
2. Significant acute comorbidity requiring urgent medical intervention
3. Signs/symptoms and parasitological confirmation of severe malaria
4. Use of any anti-malarial within the past 14 days.
5. Class I or II G6PD deficiency (defined as severe) as determined at screening
6. Pregnant or lactating female, or female of childbearing age, up to 50 years of age, who does not agree to use an acceptable form of contraception during the study
7. Clinically significant abnormal EKG, including a QTcF interval > 500 ms at enrollment.
8. Known or suspected concomitant use of QTc prolonging medications.
9. Judged by the investigator to be otherwise unsuitable for study participation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 2 patient groups

DHA-piperaquine with Primaquine

Active Comparator group

Description:

3-day treatment course of DHA-piperaquine with 45mg single dose primaquine

Treatment:

Drug: DHA-piperaquine and Primaquine

DHA-piperaquine without Primaquine

Active Comparator group

Description:

3-day treatment course of DHA-piperaquine

Treatment:

Drug: DHA-piperaquine and Primaquine