Reducing the Risk of P. Vivax After Falciparum Infections in Co-endemic Areas (PRIMA)

Menzies School of Health Research

Status and phase: Completed; Phase 4

Conditions: Vivax Malaria; Falciparum Malaria; Malaria

Treatments: Drug: primaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT03916003

19-3288

Details and patient eligibility

About

This study is designed as a multi-centre randomized, open label trial to compare the safety and efficacy of a high dose primaquine (PQ) treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice of providing only schizontocidal treatment.

Full description

Plasmodium vivax forms dormant liver stages that reactivate weeks or months following an acute infection. Recurrent infections can be associated with a febrile illness, a cumulative risk of severe anaemia, direct and indirect mortality, and are the most important source of onward transmission of the parasite. In co-endemic areas, there is a very high risk (up to 50%) of patients representing with P. vivax malaria following treatment of P. falciparum. Hence, in co-endemic regions there is a strong rationale for eradicating P. vivax hypnozoites from the liver in patients presenting with uncomplicated P. falciparum infections.

The recently completed multicentre IMPROV study compared the efficacy of a 7 day primaquine regimen (1.0 mg/kg/day for 7 days) with a 14 day regimen (0.5 mg/kg/day for 14 days). The 7 day PQ regimen was non-inferior to the 14 day regimen and 5-fold more efficacious at reducing P. vivax recurrence than the control.

This study is designed as a multicentre randomized, open label trial to compare the safety and efficacy of a high dose PQ treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice of providing only schizontocidal treatment.

Enrollment: 500 patients

Sex: All

Ages: 1+ year old

Volunteers: No Healthy Volunteers

Inclusion criteria

• P. falciparum mono-infection
• Fever (axillary temperature ≥37.5⁰C) or history of fever in preceding 48 hours
• Age >1 years (≥ 18 years at the Ethiopia site)
• G6PD normal as defined by the Biosensor (SD Biosensor, ROK) at ≥70% of the adjusted male median (AMM) for each site
• Written informed consent
• Able to comply with all study procedures and timelines

Exclusion criteria

• General danger signs or symptoms of severe malaria
• Anaemia, defined as Hb <8g/dl
• Pregnant women as determined by Urine β-HCG pregnancy test
• Breast feeding women
• Known hypersensitivity to any of the drugs given
• Regular use of drugs with haemolytic potential
• Blood transfusion within the last 4 months

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

500 participants in 2 patient groups

PQ7

Experimental group

Description:

high dose primaquine regimen over 7 days (1.0 mg/kg/day for 7 days)

Treatment:

Drug: primaquine

standard care

No Intervention group

Description:

As per national guidelines for P. falciparum treatment