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

This study has been completed.
Sponsor:
Collaborator:
Wellcome Trust
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier:
NCT01365598
First received: June 1, 2011
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Falciparum Malaria
Drug: Primaquine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Evaluation of the Efficacy and Safety of Primaquine for Clearance of Gametocytes in Uncomplicated Falciparum Malaria in Uganda

Resource links provided by NLM:


Further study details as provided by London School of Hygiene and Tropical Medicine:

Primary Outcome Measures:
  • Mean number of days to gametocyte clearance (gametocyte clearance time, GCT) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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.

  • Mean (+/- SD) maximal fall in Hb (g/dL) from enrollment to day 28 of follow-up [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Mean maximal greatest negative difference in Hb (measured by Hemocue®) from enrollment value per treatment arm over 28 days follow up


Secondary Outcome Measures:
  • Mean (+/- SD) area under the curve of gametocyte density per day during 14 days of follow-up [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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

  • Requirement for blood transfusion [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Percentage of children receiving blood transfusion per treatment arm during days 0-28

  • Follow-up day of Hb nadir [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Mean day of follow up (day 0-28) per treatment arm of lowest Hb measurement (by Hemocue®)

  • Incidence of serious adverse events by sign, symptom, laboratory parameter and relationship to taking study drug [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Percentage (number) per treatment arm during days 0-28

  • Incidence of gastrointestinal symptoms after taking study drug [ Time Frame: 6 days ] [ Designated as safety issue: Yes ]
    Percentage (number) of children with gastrointestinal symptoms per treatment arm during days 2-7


Enrollment: 468
Study Start Date: December 2011
Study Completion Date: May 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Non-active drug
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).
Other Name: primaquine phosphate
Experimental: Low dose primaquine (PQ1)
Lowest experimental dose of primaquine base: 0.1mg/kg
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).
Other Name: primaquine phosphate
Experimental: Intermediate dose primaquine (PQ2)
Intermediate experimental dose of primaquine base: 0.4mg/kg
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).
Other Name: primaquine phosphate
Active Comparator: Reference dose primaquine (PQ-R)
WHO-recommended dose of primaquine base: 0.75mg/kg
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).
Other Name: primaquine phosphate

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.

  Eligibility

Ages Eligible for Study:   1 Year to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01365598

Locations
Uganda
Walukuba Health Centre IV
Jinja, Eastern Region, Uganda
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Wellcome Trust
Investigators
Principal Investigator: Alice C Eziefula, MBBS MCRP MRCPath London School of Hygiene and Tropical Medicine
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT01365598     History of Changes
Other Study ID Numbers: PQPF912
Study First Received: June 1, 2011
Last Updated: June 11, 2013
Health Authority: Uganda: National Drug Authority

Keywords provided by London School of Hygiene and Tropical Medicine:
malaria
uncomplicated malaria
gametocytocidal drug
gametocytocidal
gametocyte
primaquine
transmission blocking
malaria transmission
sexual parasite
sexual stage
Uganda
Africa

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Primaquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014