Safety and Efficacy of Primaquine for P. Vivax

NCT01837992 | Unknown DMC

• 1 other identifier: VanSI_2013
• Study Type: interventional
• Target: 180
• Locations: 2 countries
• Sites: 4

Brief Summary

The Melanesian states of the Western Pacific (Papua New Guinea, Solomon Islands and Vanuatu) represent a unique and especially prescient challenge to malaria control and elimination. While the use of bed nets and other vector control and case management measures have achieved major advances in overall malaria control, the P. vivax and P. ovale species account for an ever-increasing burden of clinical disease. The lack of effective treatment of the hypnozoite stages of infection with these species result in ongoing relapses and a continuing reservoir of infection. The only known drug effective for treatment of the hypnozoite stage is primaquine; however the safe and effective dose of this drug in malaria treatment is still unclear. A recent study evaluated the safety and efficacy of two primaquine dosing regimens (0.25mg/kg and 0.5mg/kg) in a population in New Ireland province, PNG. This study aims to replicate this methodology in Vanuatu and Solomon Islands, to provide a more complete picture of primaquine efficacy and safety in each of the three countries of this region.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• Efficacy: Numbers of Plasmodium vivax relapses per person-years of follow-

  Total number of microscopically diagnosed (including both symptomatic and asymptomatic infections), PCR-confirmed relapses with Plasmodium vivax in participants in each treatment arm over the 3-month follow-up period, expressed as number of relapses per person-years of follow-up.

  12 months

Secondary Outcomes (6)

• Safety and toxicity (1): Numbers with mild adverse events

  12 months

• Safety and toxicity (2) Numbers with moderate adverse events

  12 months

• Safety and toxicity (3) Numbers with severe adverse events

  12 months

• Safety and toxicity (4) Numbers with any adverse events

  12 months

• Safety and toxicity (5) Numbers with assumed significant haemolysis

  12 months

Study Arms (3)

Standard dose

ACTIVE COMPARATOR

Participants will receive a standard 3-day treatment course of artemether-lumefantrine at the standard age-based dosage, and will be administered the standard recommended primaquine dose of 0.25mg/kg for 14 consecutive days.

Drug: Primaquine

High dose

ACTIVE COMPARATOR

Participants will receive a standard 3-day treatment course of artemether-lumefantrine at the standard age-based dosage, and will be administered a primaquine dose of 0.5mg/kg/day for 14 consecutive days.

Drug: Primaquine

Control

OTHER

Participants will receive a standard 3-day treatment course of artemether-lumefantrine at the standard age-based dosage, but will not receive primaquine until the time of confirmed recurrent parasitaemia or completion of 3 months follow up.

Drug: delayed primaquine

Interventions

Primaquine DRUG

High dose; Standard dose

delayed primaquine DRUG

Control

Eligibility Criteria

• Age: 12 Months - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 12 months to 60 years
• Melanesian background and living in local area
• Microscopically (based on field microscopy) or RDT confirmed P.vivax regardless of parasite density. Mixed infections (P.falciparum-P.vivax and P.malariae-P.vivax) can be included.

You may not qualify if:

• Any signs of severe malaria (see WHO definitions) including: impaired consciousness, respiratory distress, severe anaemia (Hb\<5), multiple seizures, frequent vomiting/ inability to swallow tablets, prostration, jaundice, hypotension, abnormal bleeding or hypoglycaemia.
• Clinical evidence of non-malarial illness (such as pneumonia or otitis media)
• Severe malnutrition (weight-for-age nutritional Z score \[WAZ\] \<60th percentile)
• Permanent disability, which prevents or impedes study participation.
• Treatment with primaquine in the previous 14 days
• Residence or planned travel outside the study area during the follow-up period (precluding supervised treatment and follow-up procedures)
• Known or suspected pregnancy
• Currently breastfeeding
• A positive rapid test for G6PD deficiency (Binax or Carestart RDT)

Sponsors & Collaborators

• Menzies School of Health Research: lead
• Walter and Eliza Hall Institute of Medical Research: collaborator
• Ministry of Health, Vanuatu: collaborator
• Ministry of Health, Solomon Islands: collaborator
• World Health Organization: collaborator

Study Sites (4)

Tetere Hospital, Guadalcanal Province

Honiara, Guadalcanal Province, Solomon Islands

Location

Aoki Hospital, Malaita Province

Auki, Malaita Province, Solomon Islands

Location

Northern Provincial Hospital, Nambauk Aid Post, V.F.H.A Dispensary and Fanafo Dispensary

Luganville, Sanma, Vanuatu

Location

Toroa Dispensary, NTM Health Centre and Vila Central Hospital

Port Vila, Shefa Province, Vanuatu

Location

MeSH Terms

Conditions

Malaria

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

Central Study Contacts

Ivo Mueller, PhD

CONTACT

+61 3 9345 2555; mueller@wehi.edu.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: April 23, 2013
• Study Start: May 1, 2013
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2015
• Last Updated: November 8, 2013

Record last verified: 2013-11

Locations

VA (2); SO (2)