Dihydroartemisinin-piperaquine and Primaquine for Uncomplicated Plasmodium Falciparum Cases

Study Overview
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Brief Summary
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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
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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:

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

Conditions
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Malaria

Intervention / Treatment
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* Drug: dihydroartemisinin-piperaquine
* Drug: dihydroartemisinin-piperaquine + primaquine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: dihydroartemisinin-piperaquine<br> | Drug: dihydroartemisinin-piperaquine<br>* 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.<br>* Other names: DHP;|
| Active Comparator: Dihydroartemisininpiperaquine primaquine<br> | Drug: dihydroartemisinin-piperaquine + primaquine<br>* 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.<br>* Other names: DHP, PQ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of sexual stages of P.falciparum | 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. | 42 days post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance of asexual stages P.falciparum | 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. | 42 days post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malaria, DHP, PQ, gametocytes