Dihydroartemisinin-piperaquine With Low Dose Primaquine to Reduce Malaria Transmission

NCT02259426 | Completed Phase 3 DMC

• 1 other identifier: DAPPI-1
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Primaquine (PQ) is currently the only available drug that can clear the mature transmission stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist after artemisinin-combination therapy. A major caveat to the use of primaquine in mass adminsitrations for the reduction of malaria transmission is that metabolism of the drug in individuals with glucose-6 phosphate dehydrogenase (G6PD) deficiency can lead to transient haemolysis. The haemolytic side effect of PQ is dose-related. Haemolysis is more commonly observed after prolonged PQ treatment but has also been observed in African populations following a single dose of PQ. This haemolysis was self-limiting, largely restricted to G6PD deficient individuals and did not lead to clinical symptoms. Nevertheless, any drug-induced haemolysis is reason for concern and the World Health Organization has therefore reduced the recommended dose of single low dose primaquine from 0.75mg/kg to 0.25mg/kg. This dosage is deemed safe without prior G6PD or Hb screening. However, there is limited direct evidence on the extent to which this dosage of PQ prevents malaria transmission to mosquitoes. In the current study, the investigators will assess the efficacy of DP in combination with low-dose PQ to prevent onward malaria transmission. The investigators will perform the investigators study in individuals aged 5-15 years who are carry microscopically detectable densities of P. falciparum gametocytes. This age group is chosen because asexual parasite carriage and gametocyte carriage are common in this age group. All enrolled individuals will receive a full three-day course of DP, and will be randomized to receive a dose of primaquine or placebo with their third dose. Efficacy will be determined based on gametocyte carriage during follow-up, measured by molecular methods. For all individuals, the effect of treatment on infectivity to mosquitoes will be assessed by membrane feeding assays at two time points.

Conditions

Malaria; Asymptomatic Malaria; Plasmodium Falciparum

Outcome Measures

Primary Outcomes (1)

• Gametocyte prevalence on day 7 after initiation of treatment

  Gametocyte prevalence on day 7 after initiation of treatment is measured by molecular methods.

  day 7 of follow-up

Secondary Outcomes (4)

• Transmission to Anopheles gambiae mosquitoes

  Day 3 and 7 during follow-up

• Haematological recovery

  14 days during follow-up

• Gametocyte sex-ratio

  14 days of follow-up

• Gametocyte carriage during follow-up

  14 days during follow-up

Study Arms (2)

Dihydroartemisínin-piperaquine (Artekin)

ACTIVE COMPARATOR

Dihydroartemisínin-piperaquine combination alone

Drug: Dihydroartemisinin-piperaquine combination (Artekin)

Dihydroartemisinin-piperaquine, Primaquine

EXPERIMENTAL

Dihydroartemisinin-piperaquine with single-dose 0.25mg/kg Primaquine

Drug: Dihydroartemisinin-piperaquine combination (Artekin); Drug: Primaquine

Interventions

Dihydroartemisinin-piperaquine combination (Artekin) DRUG

Dihydroartemisinin-piperaquine, Primaquine; Dihydroartemisínin-piperaquine (Artekin)

Primaquine DRUG

Single-dose 0.25mg/kg

Dihydroartemisinin-piperaquine, Primaquine

Eligibility Criteria

• Age: 5 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Microscopically detectable P. falciparum gametocyte carriage

You may not qualify if:

• Age \< 5 years or \> 15 years
• Non-falciparum malaria co-infection
• Malaria parasite density ≥ 200,000 parasites/µL
• Clinical symptoms indicating severe malaria
• Axillary temperature ≥ 39°C
• Body Mass Index (BMI) below 16 or above 32 kg/m2
• Haemoglobin concentration below 9.5 g/dL
• Anti-malarials taken in last 2 days
• For women: Pregnancy (assessed by clinical examination and urine pregnancy test) or lactation
• Known hypersensitivity to DP or PQ
• History and/or symptoms indicating chronic illness
• Current use of tuberculosis or anti-retroviral medication
• Unable to give written informed consent
• Unwillingness to participate in two membrane feeding assays
• Travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, - Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Radboud University Medical Center: collaborator
• International Centre of Insect Physiology and Ecology (ICIPE): collaborator

Study Sites (1)

ICIPE

Mbita, Nyanza, 30-40305, Kenya

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

Primaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Teun Bousema, PhD

  Radboud university medical center, London School of hygiene and tropical medicine

  PRINCIPAL INVESTIGATOR

• Patrick Sawa, MD

  ICIPE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2014
• First Posted: October 8, 2014
• Study Start: October 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 14, 2016

Record last verified: 2016-01

Locations

KE (1)