Dihydroartemisinin-piperaquine and Primaquine for Uncomplicated Plasmodium Falciparum Cases

NCT ID: NCT01392014

Last Updated: 2011-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 374 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2010-10-31

Brief Summary

Artemisinin-based combination therapy (ACT) has been known to be controversial for stopping malaria transmission.The addition of primaquine (PQ) - the only drug commercially available that kills mature transmission stage - to such treatments might be necessary to eliminate this stage. A study is conducted to evaluate the efficacy of dihydroartemisinin-piperaquine (DHP) regimens with or without PQ on the sexual and asexual stages of P. falciparum in Sumatra, Indonesia.

Detailed Description

The study was conducted in Hanura Primary Health Center, Padang Cermin district, Lampung province (105°45'-103°48'E and 3°45'-6°45'S) located at the southern end of Sumatra island.

The study subjects received either 3 day doses of dihydroartemisinin-piperaquine with or without 1 day of primaquine according to their body weight.

Patients with fever or history of fever within the past 24 hours were screened by microscopic examination of Giemsa-stained thick blood films to detect P. falciparum infection.

All subjects were allocated by open-label randomization to receive DHP alone (on Day 0 to Day 2) or DHP plus a single dose of PQ (Day 3). The procedures of drug administration in the study were as follows:

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

dihydroartemisinin-piperaquine

Group Type: ACTIVE_COMPARATOR

dihydroartemisinin-piperaquine

Intervention Type: DRUG

This study used fixed-dose tablets of 40 mg dihydroartemisinin and 320 mg piperaquine for each tablet (D-ARTEPP®, Guilin Pharmaceutical Co., Ltd, China. The regimen is based on weight for 3 days (D0, D1 and D2) with maximal dose of 1 x 3 tablets for patients weighing ≥ 41 kg; 1 x 2 tablets for patients weighing 31 - 40 kg, 1 x 1.5 tablets for patients weighing 18 - 30 kg, and 1 X 1 tablet for patients with body weight of 11 - 17 kg.

Dihydroartemisininpiperaquine primaquine

Group Type: ACTIVE_COMPARATOR

dihydroartemisinin-piperaquine + primaquine

Intervention Type: DRUG

For DHP, treatment was as for Arm dihydroartemisinin piperaquine. A single dose PQ of 0.75 mg/kg BW was provided on Day-3 using 15 mg base PQ tablets (local product by PT Pharos Indonesia, batch no 15306002, produced on 30/05/2008 and expiring on May 2012). The maximal dose was 3 tablets for subjects weighing ≥ 60 kg. The dose range for subjects weighing 10 - 13 kg was 0.5 tablet; 14 - 18 kg was 0.75 tablet; 19 - 23 kg was 1 tablet, 24 -30 kg was 1.5 tablet; 31 - 40 kg was 2 tablets; 41- 49 kg was 2.25 tablet; 50 - 59 kg was 2.5 tablet and ≥ 60 kg was 3 tablets.

Interventions

dihydroartemisinin-piperaquine

This study used fixed-dose tablets of 40 mg dihydroartemisinin and 320 mg piperaquine for each tablet (D-ARTEPP®, Guilin Pharmaceutical Co., Ltd, China. The regimen is based on weight for 3 days (D0, D1 and D2) with maximal dose of 1 x 3 tablets for patients weighing ≥ 41 kg; 1 x 2 tablets for patients weighing 31 - 40 kg, 1 x 1.5 tablets for patients weighing 18 - 30 kg, and 1 X 1 tablet for patients with body weight of 11 - 17 kg.

Intervention Type: DRUG

dihydroartemisinin-piperaquine + primaquine

For DHP, treatment was as for Arm dihydroartemisinin piperaquine. A single dose PQ of 0.75 mg/kg BW was provided on Day-3 using 15 mg base PQ tablets (local product by PT Pharos Indonesia, batch no 15306002, produced on 30/05/2008 and expiring on May 2012). The maximal dose was 3 tablets for subjects weighing ≥ 60 kg. The dose range for subjects weighing 10 - 13 kg was 0.5 tablet; 14 - 18 kg was 0.75 tablet; 19 - 23 kg was 1 tablet, 24 -30 kg was 1.5 tablet; 31 - 40 kg was 2 tablets; 41- 49 kg was 2.25 tablet; 50 - 59 kg was 2.5 tablet and ≥ 60 kg was 3 tablets.

Intervention Type: DRUG

Other Intervention Names

DHP; DHP, PQ

Eligibility Criteria

Inclusion Criteria

• age ≥ 4 years old
• parasite count ≥ 1,000 asexual parasites/µL
• normal glucose-6-phosphate dehydrogenase enzyme level based on qualitative test (Trinity Biotech® no 203, USA)
• hemoglobin level ≥ 8 gr/dL as measured by Hemoque® apparatus;
• have the ability to return for 42-day-follow up and
• willingness to sign the informed-consent form.

Exclusion Criteria

• are infected with other r plasmodium species
• have only gametocytes of P. falciparum;
• are pregnant - measured by positive result on HCG urine test and/or breastfeeding women
• present signs of pitting edema on both legs as a sign of malnutrition
• have complicated or severe malaria, other chronic diseases or history of drug allergies.

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indonesia University

OTHER

Sponsor Role: lead

Responsible Party

Parasitologi Fakultas Kedokteran, University of Indonesia

Principal Investigators

Inge Sutanto, MD

Role: PRINCIPAL_INVESTIGATOR

Univesity of Indonesia

Locations

Hanura Primary Health Center

Lampung, Sumatra, Indonesia

Countries

Indonesia

References

Sutanto I, Suprijanto S, Kosasih A, Dahlan MS, Syafruddin D, Kusriastuti R, Hawley WA, Lobo NF, Ter Kuile FO. The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South sumatra, Western indonesia: an open-label, randomized, controlled trial. Clin Infect Dis. 2013 Mar;56(5):685-93. doi: 10.1093/cid/cis959. Epub 2012 Nov 21.

Reference Type: DERIVED

PMID: 23175563 (View on PubMed)

Other Identifiers

45114

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

45114

Identifier Type: -

Identifier Source: org_study_id