Comparison Between 7 and 14 Day Primaquine Combined With Dihydroartemisinin-piperaquine or 3 Day Chloroquine Radical Cure of P. Vivax (BPD)

Vivax Malaria Clinical Trial

Official title:

Randomised Parallel Open Label Comparison Between 7 and 14 Day Primaquine Combined With 3-day Dihydroartemisinin-piperaquine or 3-day Chloroquine Regimens for Radical Cure of Plasmodium Vivax

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01640574
• Other study ID #: SMRU1102
• Status: Completed
• Phase: Phase 3
• First received: July 11, 2012
• Last updated: April 27, 2016
• Start date: February 2012
• Est. completion date: December 2015

Study information

• Verified date: April 2016
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

In Southeast Asia, Plasmodium vivax (Pv) infection reaches 50-80% and bears a greater burden of disease than Plasmodium falciparum (Pf). As control over Pf improves, Pv will assume increasingly larger percentages of malaria prevalence. The chronicity of Pv, due to the latent liver stage (hypnozoite) not eradicated by chloroquine, causes recurring disability and compounds the economic burden of those with symptomatic disease. The only widely available treatment for hypnozoites is primaquine, which, because of challenges with tolerability, safety in G6PD deficient persons, and compliance, is not commonly prescribed for the treatment of Pv. Currently, chloroquine is used for the treatment of the blood stages of Pv, however, there are concerns about increasing parasite resistance. Alternative treatments, such as artesunate, should be considered in the future of the treatment of blood stage Pv. The use of primaquine in the treatment of hypnozoites (radical cure) should be emphasized so that transmission of Pv can be controlled.

This study aims to determine the optimal primaquine regimen for radical cure of Plasmodium vivax. Chloroquine is currently the standard of treatment for Plasmodium vivax. Chloroquine may have synergistic effects when used with primaquine and due to its long half-life may delay the first relapse of vivax malaria. In contrast, artesunate does not have documented interactions with primaquine and has a very short half-life, thus, presumably will have no impact on first relapse. Combining primaquine with these two anti-malarials may lead to an alternative regimen for Pv infection and changing the primaquine dosing regimen may lead to a more practical and efficacious therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 680
• Est. completion date: December 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months and older

Eligibility

Inclusion Criteria:

• = 6 months old

• Microscopic diagnosis of Plasmodium vivax malaria mono-infection

• Participant or parent/guardian is willing and able to give informed consent for participation in the study

• Able (in the Investigators opinion) and willing to comply with all study requirements.

Exclusion Criteria:

• Severe malaria

• History of allergy or adverse reaction to artesunate, piperaquine, chloroquine, or primaquine

• Blood transfusion in the past 3 months

• G6PD deficiency by rapid test

• Hematocrit = 25%

• Pregnancy at the time of screening

• Breastfeeding an infant < 6 months old

• Presence of any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria, Vivax
• Vivax Malaria

Intervention

Drug:
• Dihydroartemisinin-Piperaquine
Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days and Primaquine 1 mg/kg once daily for 7 days
• Dihydroartemisinin-Piperaquine
Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days Primaquine 0.5 mg/kg daily for 14 days
• Chloroquine
Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days
• Chloroquine
o Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days

Locations

Country	Name	City	State
Thailand	Shoklo Malaria Research Unit	Mae Sot	Tak

Sponsors (1)

Lead Sponsor	Collaborator
University of Oxford

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence of P. vivax	Recurrence with Plasmodium vivax malaria within 52 weeks of first treatment dose	52 weeks	No
Secondary	Adverse Events	Number of adverse events within 28 days of study medication	28 days	Yes
Secondary	Recurrence of P. vivax	Recurrence with Plasmodium vivax malaria within 6 months of first treatment dose	6 months	No
Secondary	Drug concentrations	Chloroquine, piperaquine and primaquine drug levels	63 days	No