DHP+PQ: Dihydroartemisinin-piperaquine and Primaquine for Uncomplicated Plasmodium Falciparum Cases

Sponsor

Indonesia University (Other)

Overall Status

Completed

CT.gov ID

NCT01392014

Collaborator

(none)

374

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Drug: dihydroartemisinin-piperaquine Drug: dihydroartemisinin-piperaquine + primaquine	Phase 4

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:

Study Design

Study Type:

Interventional

Actual Enrollment :

374 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Effectiveness of Dihydroartemisinin-piperaquine With or Without Primaquine on Gametocytes Plasmodium Falciparum in Mesoendemic Area of Indonesia

Study Start Date :

Dec 1, 2008

Actual Primary Completion Date :

Mar 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: dihydroartemisinin-piperaquine	Drug: 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. Other Names: DHP
Active Comparator: Dihydroartemisininpiperaquine primaquine	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. Other Names: DHP, PQ

Arm

Intervention/Treatment

Active Comparator: dihydroartemisinin-piperaquine

Drug: 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.

Other Names:

DHP

Active Comparator: Dihydroartemisininpiperaquine primaquine

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.

Other Names:

DHP, PQ

Outcome Measures

Primary Outcome Measures

Development of sexual stages of P.falciparum [42 days post treatment]
Finger prick blood samples are collected for malaria blood smear. Thick and thin blood smears were stained with 3% Giemsa solution for 40 minutes and were read under binocular microscope with 1,000X magnification.

Secondary Outcome Measures

Clearance of asexual stages P.falciparum [42 days post treatment]
Finger prick blood samples are collected for malaria blood smear. Thick and thin blood smears were stained with 3% Giemsa solution for 40 minutes and were read under binocular microscope with 1,000X magnification.

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.