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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01365598
Other study ID # PQPF912
Secondary ID
Status Completed
Phase Phase 3
First received June 1, 2011
Last updated June 11, 2013
Start date December 2011
Est. completion date May 2013

Study information

Verified date June 2013
Source London School of Hygiene and Tropical Medicine
Contact n/a
Is FDA regulated No
Health authority Uganda: National Drug Authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of lower doses of primaquine compared to the dose recommended by the WHO for reducing P. falciparum gametocytes in the infected human host to prevent transmission of falciparum malaria to the anopheles mosquito vector.


Description:

A single dose of 0.75mg/kg primaquine base is recommended by the WHO to block transmission of falciparum malaria from infected humans to mosquitoes by clearing gametocytes. However, the optimal dose for safety and efficacy has not been evaluated. Dose-finding data is important because primaquine has a dose-dependent risk of causing haemolysis (destruction of blood cells) in pre-disposed individuals, such as those with G6PD deficiency. G6PD deficiency is most prevalent in malaria-endemic areas. Therefore, it is essential that data on primaquine's safety is available in such areas.

The investigators hypothesise that lower doses of primaquine have a lower risk of adverse effects compared to the WHO-recommended dose, but retain the transmission-blocking efficacy.

The investigators propose to test this hypothesis in a four-arm clinical trial with a non-inferiority design to evaluate the efficacy and a superiority design to evaluate the safety of the WHO dose (0.75mg/kg) and lower doses of primaquine for clearance of P. falciparum gametocytes in children in Uganda. The study will include a pharmacokinetic analysis.


Recruitment information / eligibility

Status Completed
Enrollment 468
Est. completion date May 2013
Est. primary completion date March 2013
Accepts healthy volunteers No
Gender Both
Age group 1 Year to 10 Years
Eligibility Inclusion Criteria:

- Age >/= 1 year and </= 10 years

- Weight over 10kg

- Fever >38 degrees C (tympanic) or history of fever in the last 24 hours

- P. falciparum parasitaemia <500 000/µl

- Normal G6PD enzyme function

Exclusion Criteria:

- Enrolled in another study

- Evidence of severe illness/ danger signs

- Known allergy to study medications

- Haemoglobin < 8g/dL)

- Started menstruation

- Pregnancy or breastfeeding

- Primaquine taken within the last 4 weeks

- Blood transfusion within the last 90 days

- Non-falciparum malaria co-infection

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Prevention


Related Conditions & MeSH terms


Intervention

Drug:
Primaquine
Single dose of oral primaquine phosphate. Comparator dose is 0.75mg/kg primaquine base. Each experimental arm is a different (reduced) dose of primaquine phosphate. Placebo contains no primaquine phosphate (non-active ingredients only).

Locations

Country Name City State
Uganda Walukuba Health Centre IV Jinja Eastern Region

Sponsors (2)

Lead Sponsor Collaborator
London School of Hygiene and Tropical Medicine Wellcome Trust

Country where clinical trial is conducted

Uganda, 

References & Publications (5)

Bousema T, Okell L, Shekalaghe S, Griffin JT, Omar S, Sawa P, Sutherland C, Sauerwein R, Ghani AC, Drakeley C. Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs. Malar J. 2010 May 24;9:136. doi: 10.1186/1475-2875-9-136. — View Citation

Schneider P, Bousema JT, Gouagna LC, Otieno S, van de Vegte-Bolmer M, Omar SA, Sauerwein RW. Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection. Am J Trop Med Hyg. 2007 Mar;76(3):470-4. — View Citation

Shekalaghe S, Drakeley C, Gosling R, Ndaro A, van Meegeren M, Enevold A, Alifrangis M, Mosha F, Sauerwein R, Bousema T. Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS One. 2007 Oct 10;2(10):e1023. — View Citation

Shekalaghe SA, ter Braak R, Daou M, Kavishe R, van den Bijllaardt W, van den Bosch S, Koenderink JB, Luty AJ, Whitty CJ, Drakeley C, Sauerwein RW, Bousema T. In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrob Agents Chemother. 2010 May;54(5):1762-8. doi: 10.1128/AAC.01135-09. Epub 2010 Mar 1. — View Citation

Smithuis F, Kyaw MK, Phe O, Win T, Aung PP, Oo AP, Naing AL, Nyo MY, Myint NZ, Imwong M, Ashley E, Lee SJ, White NJ. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect Dis. 2010 Oct;10(10):673-81. doi: 10.1016/S1473-3099(10)70187-0. Epub 2010 Sep 9. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Mean number of days to gametocyte clearance (gametocyte clearance time, GCT) Mean number of days per treatment arm for gametocytes to become undetectable using sub-microscopic molecular testing methods (real-time nucleic acid sequence-based amplification, QT-NASBA)and interpolated from measured data points. 14 days No
Primary Mean (+/- SD) maximal fall in Hb (g/dL) from enrollment to day 28 of follow-up Mean maximal greatest negative difference in Hb (measured by Hemocue®) from enrollment value per treatment arm over 28 days follow up 28 days Yes
Secondary Mean (+/- SD) area under the curve of gametocyte density per day during 14 days of follow-up An estimate of the area under the curve of gametocytes (measured by QT-NASBA) seen over time, averaged per day of follow up (days 0-14) and interpolated from measured data points 14 days No
Secondary Requirement for blood transfusion Percentage of children receiving blood transfusion per treatment arm during days 0-28 28 days Yes
Secondary Follow-up day of Hb nadir Mean day of follow up (day 0-28) per treatment arm of lowest Hb measurement (by Hemocue®) 28 days Yes
Secondary Incidence of serious adverse events by sign, symptom, laboratory parameter and relationship to taking study drug Percentage (number) per treatment arm during days 0-28 28 days Yes
Secondary Incidence of gastrointestinal symptoms after taking study drug Percentage (number) of children with gastrointestinal symptoms per treatment arm during days 2-7 6 days Yes
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