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Falciparum MalariaPhase 3NCT01365598

Evaluation of the Gametocytocidal Efficacy and Safety of Primaquine in Uncomplicated Falciparum Malaria in Uganda

A Phase 3 study testing Primaquine in people with Falciparum Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Uganda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 1 year to 10 years
Conditions the study is for
Falciparum Malaria
What is being tested?
Primaquine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
468 participants
Where
1 siteUganda
Study dates
Dec 2011to May 2013
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 10 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • Enrolled in another study
  • Evidence of severe illness/ danger signs
  • Known allergy to study medications
  • Haemoglobin < 8g/dL)
  • Started menstruation
  • Pregnancy or breastfeeding
Show all 9Show fewer
  • Primaquine taken within the last 4 weeks
  • Blood transfusion within the last 90 days
  • Non-falciparum malaria co-infection

Trial locations and contacts

1 site in 1 country.

Uganda1 site

  • Walukuba Health Centre IV

    Jinja, Eastern Region

Other trials in Uganda

About this study

Official title: Evaluation of the Efficacy and Safety of Primaquine for Clearance of Gametocytes in Uncomplicated Falciparum Malaria in Uganda

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.

Read the detailed 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.

Being tested
Primaquine
Keywords
malaria, uncomplicated malaria, gametocytocidal drug, gametocytocidal, gametocyte, primaquine, transmission blocking, malaria transmission, sexual parasite, sexual stage, Uganda, Africa
Medical subject headings
Malaria, Falciparum, Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PrimaquineDrug

    Also called primaquine phosphate

    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).

Study groups in NCT01365598
Study groupRoleWhat they receive
PlaceboPlacebo comparatorNon-active drug
Receives: Drug: Primaquine
Low dose primaquine (PQ1)ExperimentalLowest experimental dose of primaquine base: 0.1mg/kg
Receives: Drug: Primaquine
Intermediate dose primaquine (PQ2)ExperimentalIntermediate experimental dose of primaquine base: 0.4mg/kg
Receives: Drug: Primaquine
Reference dose primaquine (PQ-R)Active comparatorWHO-recommended dose of primaquine base: 0.75mg/kg
Receives: Drug: Primaquine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 14 days

  2. 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

    Measured: 28 days

Secondary outcomes (5)

  1. 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

    Measured: 14 days

  2. Requirement for blood transfusion

    Percentage of children receiving blood transfusion per treatment arm during days 0-28

    Measured: 28 days

  3. Follow-up day of Hb nadir

    Mean day of follow up (day 0-28) per treatment arm of lowest Hb measurement (by Hemocue®)

    Measured: 28 days

  4. 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

    Measured: 28 days

  5. Incidence of gastrointestinal symptoms after taking study drug

    Percentage (number) of children with gastrointestinal symptoms per treatment arm during days 2-7

    Measured: 6 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionMar 2013
  4. Study completionMay 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
468 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01365598
Sponsor's protocol ID
PQPF912
Status last verified
Jun 2013
First submitted
1 Jun 2011
Last updated
12 Jun 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 20497536

  • 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. doi: 10.1371/journal.pone.0001023.

    PubMed 17925871

  • 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.

    PubMed 17360869

  • 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.

    PubMed 20194698

  • 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.

    PubMed 20832366

  • Chang HH, Meibalan E, Zelin J, Daniels R, Eziefula AC, Meyer EC, Tadesse F, Grignard L, Joice RC, Drakeley C, Wirth DF, Volkman SK, Buckee C, Bousema T, Marti M. Persistence of Plasmodium falciparum parasitemia after artemisinin combination therapy: evidence from a randomized trial in Uganda. Sci Rep. 2016 May 20;6:26330. doi: 10.1038/srep26330.

    PubMed 27197604

  • Eziefula AC, Bousema T, Yeung S, Kamya M, Owaraganise A, Gabagaya G, Bradley J, Grignard L, Lanke KH, Wanzira H, Mpimbaza A, Nsobya S, White NJ, Webb EL, Staedke SG, Drakeley C. Single dose primaquine for clearance of Plasmodium falciparum gametocytes in children with uncomplicated malaria in Uganda: a randomised, controlled, double-blind, dose-ranging trial. Lancet Infect Dis. 2014 Feb;14(2):130-9. doi: 10.1016/S1473-3099(13)70268-8. Epub 2013 Nov 13.

    PubMed 24239324

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Primaquine in people with Falciparum Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Uganda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean number of days to gametocyte clearance (gametocyte clearance time, GCT) (time frame: 14 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01365598, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2013.

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