DHA-PQP vs Chloroquine and Primaquine for Radical Cure of Vivax Malaria in Brazil

NCT03208907 | Completed Phase 3 DMC

• 1 other identifier: CAAE: 69476017.3.0000.0005
• Study Type: interventional
• Target: 419
• Locations: 1 country
• Sites: 1

Brief Summary

Plasmodium vivax can be cause of severe malaria and mortality. There are serious public health implications associated with cases of P. vivax resistant to Chloroquine in the Americas as well there are efforts of many countries to eliminate this disease. In this way, it is critically important to evaluate an alternative radical cure treatment efficient to amazon scenario. The objectives of this trial are to demonstrate the superiority of adequate parasitological response at D42 of Dihydroartemisinin plus Piperaquine (DHA-PQP or Eurartesim®) versus Chloroquine and to evaluate the proportion of failure until D180 considering different starting days of Primaquine (0.50 mg/kg/day) for 14 days. It is an open, 4 arms, randomised, comparative trial. Total of 460 patients are initially planned to be included. To demonstrate the superiority of DHA-PQP compared to Chloroquine, the 95% confidence interval of the difference observed between both treatment success rates will be determined. Each recurrence will be passively and actively detected for 180 days.

Conditions

Malaria, Vivax; Therapeutics

Keywords

Vivax malaria; Radical cure; Elimination

Outcome Measures

Primary Outcomes (2)

• Number of participants with negative parasitological test (schizonticidal therapy evaluation)

  Schizonticidal efficacy will be assessed based on the absence of Vivax Plasmodium parasites in blood of the participants, confirmed by microscopy.

  Day 42

• Number of participants with negative parasitological test (nonrelapse therapy evaluation)

  Nonrelapse therapy efficacy will be assessed based on the absence of Vivax Plasmodium parasites in blood, confirmed by microscopy.

  Day 180

Secondary Outcomes (4)

• Number of participants with negative parasitological test

  6 months (for this analysis will not be considered the primary outcomes dates (Day42 and D180)

• Number of participants with any biological intolerability

  Until Day 28

• Number of participants with any treatment-related adverse event of clinical tolerability

  6 months

• Number of participants with treatment-related prolonged QT interval.

  Day 3

Study Arms (4)

CQ coadministered with PQ

ACTIVE COMPARATOR

Chloroquine was administered for 3 days according to the brazilian protocol and Primaquine was administered for 14 days (0.50mg/kg/day)

Drug: CQ coadministered with PQ

DHA-PQP coadministered with PQ

EXPERIMENTAL

Dihydroartemisinin/Piperaquine was administered according to the weight and Primaquine (0.50mg/kg/day)

Drug: DHA-PQP coadministered with PQ

CQ and PQ starting on Day 42

EXPERIMENTAL

Chloroquine was administered for 3 days according to the brazilian protocol and Primaquine started on Day 42 for 14 days (0.50mg/kg/day) \[arm halted after preliminary analysis\]

Drug: CQ and PQ starting on Day 42

DHA-PQP and PQ starting on Day 42

EXPERIMENTAL

Dihydroartemisinin/Piperaquine was administered for 3 days according to the weight and Primaquine started on Day 42 for 14 days (0.50mg/kg/day) \[arm halted after preliminary analysis\]

Drug: DHA-PQP and PQ starting on Day 42

Interventions

CQ coadministered with PQ DRUG

113 subjects in a 3-day regimen treatment with the schizonticidal drug Chloroquine concomitantly to 14-day regimen treatment with Primaquine in a dose of 0.50 mg/kg/day.

Also known as: Standard treatment with potential synergy

CQ coadministered with PQ

DHA-PQP coadministered with PQ DRUG

In this treatment group, 112 subjects took DHA-PQP for three days and Primaquine for 14 days in the following dose: 0.50 mg/kg/day.

Also known as: Experimental treatment with potential synergy

DHA-PQP coadministered with PQ

CQ and PQ starting on Day 42 DRUG

98 subjects in a 3-day regimen treatment with Chloroquine with a 14-day regimen treatment with Primaquine in a dose of 0.50 mg/kg/day starting on Day 42 after first dose of the schizonticidal drug.

Also known as: Standard treatment with no potential synergy

CQ and PQ starting on Day 42

DHA-PQP and PQ starting on Day 42 DRUG

95 subjects in a 3-day regimen treatment with DHA-PQP with a 14-day regimen treatment with Primaquine in a dose of 0.50 mg/kg/day starting on Day 42 after first dose of the schizonticidal drug.

Also known as: Experimental treatment with no potential synergy

DHA-PQP and PQ starting on Day 42

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults and children over 6 months old (bodyweight\>5 kg)
• Body weight ≥5 kg and \<100 kg (or above, upon justification of the investigator);
• Biologically confirmed symptomatic Monoinfection by Plasmodium vivax, with parasite density between 100 and 100,000;
• Efficient activity of the enzyme Glucose-6-Phosphate Dehydrogenase (G6PD);
• Conditions for oral treatment;
• Plans known to remain in the area of the research center during the follow-up period (180 days);
• Hemoglobin concentration (Hb) at baseline\> 7g / dL.
• If the patient engage in sexual activity that could lead to pregnancy, women should use a form of contraception. At least one of the following methods should be used properly:
• Condoms (male or female) with or without spermicidal agent; Diaphragm or cervical cap with spermicide Intrauterine device (IUD) Hormonal contraceptive Ligation Tubal microimplants i. Women with no reproductive potential, as defined above, are without the use of contraceptives.
• j. Ability and willingness of the participant or legal guardian to provide free and informed consent in writing. Children who are able to understand the goals and risks of the study will sign a consent form.

You may not qualify if:

• Withdrawal of consent;
• The researcher's opinion, based on the risk and benefit assessment of the study;
• Detection of mixed infection by malaria;
• Women who become pregnant by the 63rd day of follow-up;
• Women of childbearing age who give up using effective contraception during the first 63 days of follow-up study;
• Discontinuation of blood schizonticidal treatment for any reason.

Sponsors & Collaborators

• Fundação de Medicina Tropical Dr. Heitor Vieira Dourado: lead
• Ministry of Health, Brazil: collaborator
• Oswaldo Cruz Foundation: collaborator

Study Sites (1)

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

Manaus, Amazonas, 69040000, Brazil

Location

MeSH Terms

Conditions

Malaria, Vivax

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Marcus VG de Lacerda, MD, PhD

  Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: July 6, 2017
• Study Start: July 5, 2018
• Primary Completion: July 2, 2021
• Study Completion: July 2, 2021
• Last Updated: June 12, 2023

Record last verified: 2023-06

Locations

BR (1)