Clinical trial NCT03916003: Reducing the Risk of P. Vivax After Falciparum Infections in Co-endemic Areas
Official title: Reducing the Risk of P. Vivax After Falciparum Infections in Co-endemic Areas - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Vivax Malaria
Falciparum Malaria
Lead sponsor: Menzies School of Health Research
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Tribhuvan University, Nepal
name: Arba Minch University
name: Addis Ababa University
First posted: 2019-04-16
Enrollment: 500
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence risk of any P. vivax parasitaemia at day 63
timeFrame: 63 days
Secondary outcomes:
measure: Incidence risk of symptomatic P. vivax parasitaemia at day 63
timeFrame: 63 days
measure: Incidence risk of all any P. vivax parasitaemia at day 28 and 42
timeFrame: 28 and 42 days
measure: Incidence risk of any P. falciparum malaria at day 28, 42 and 63
timeFrame: 28/42/63 days
measure: proportion of patients vomiting their medication within 1 hour of administration
timeFrame: 1 hour
measure: proportion of patients vomiting any of their PQ doses within 1 hour of administration
timeFrame: 7 days
measure: proportion of adverse events and serious adverse events
timeFrame: 63 days
measure: incidence risk of severe anaemia (Hb<5g/dl) and moderately severe anaemia (<7g/dl) and/or the risk for blood transfusion between day 3 and 7
timeFrame: 7 days
measure: • The incidence risk of ≥25% fall in haemoglobin since baseline with and without hemoglobinuria at day 3 and day 7
timeFrame: 7 days
measure: The incidence risk of ≥25% fall in haemoglobin to under 7g/dl with and without hemoglobinuria at day 3 and day 7
timeFrame: day 7
measure: Incidence risk of P. falciparum gametocytaemia between day 7 and 63
timeFrame: 63 days
measure: Parasite clearance on day 1, 2 and 3
timeFrame: 3 days
measure: Fever clearance on day 1, 2 and 3
timeFrame: 3 days
Other outcomes:
Locations:
city: Upazila
country: Bangladesh
facility: Icddrb
city: Arba Minch
country: Ethiopia
facility: Arba Minch University
city: Dusun Tenggara
country: Indonesia
facility: Puskesmas Mangili
Study officials:
affiliation: Menzies School of Health Research
name: Kamala Thriemer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thriemer K, Degaga TS, Christian M, Alam MS, Ley B, Hossain MS, Kibria MG, Tego TT, Abate DT, Weston S, Karahalios A, Rajasekhar M, Simpson JA, Rumaseb A, Mnjala H, Lee G, Anose RT, Kidane FG, Woyessa A, Baird K, Sutanto I, Hailu A, Price RN. Reducing the risk of Plasmodium vivax after falciparum infections in co-endemic areas-a randomized controlled trial (PRIMA). Trials. 2022 May 18;23(1):416. doi: 10.1186/s13063-022-06364-z.