Clinical trial NCT04079621: Short Course Radical Cure of P. Vivax Malaria in Nepal
Official title: Short Course Radical Cure of P.Vivax in Nepal- a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Malaria, Vivax
Malaria,Falciparum
Lead sponsor: Menzies School of Health Research
Sponsor class: OTHER
Collaborators: name: Tribhuvan University, Nepal
First posted: 2019-09-06
Enrollment: 27
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 multicentre randomized, open label trial to assess the safety and efficacy of a low dose short course PQ treatment (3.5mg/kg total dose given over 7 days) in glucose-6-phosphate dehydrogenase (G6PD) normal patients with P.vivax and P falciparum to reduce the risk of subsequent P.vivax episodes.

Detailed description: Plasmodium vivax is associated with recurrent infections weeks or months following the acute infection due to reactivation of dormant liver stages. Recurrent infections can be associated with a febrile illness, 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 PQ regimen (1.0mg/kg/day for 7 days) with a 14 day regimen (0.5mg/kg/day for 14 days). The 7 day PQ regimen was non-inferior to the 14 day regimen and 5 times more efficacious at reducing P.vivax recurrence than the control.

This study is designed as a multicentre randomized, open label trial to assess the safety and efficacy of a low dose short course PQ treatment (3.5mg/kg total dose given over 7 days) in G6PD normal patients with P.vivax and P falciparum to reduce the risk of subsequent P.vivax episodes.

Eligibility criteria: Inclusion Criteria:

* P. falciparum and/or vivax infection
* Fever (axillary temperature ≥37.5⁰C) or history of fever in preceding 48 hours
* Age \>1 years
* G6PD normal by Rapid Diagnostic Test (RDT) as per national guidelines
* 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 P. vivax relapse at month 6
timeFrame: 6 months
Secondary outcomes:
measure: The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. vivax
timeFrame: 6 months
measure: The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. falciparum
timeFrame: 6 month
measure: The incidence risk of symptomatic P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection
timeFrame: Day 28
measure: The incidence risk of all (symptomatic and asymptomatic) P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection
timeFrame: Day 28
measure: The incidence risk of asymptomatic P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection
timeFrame: Day 28
Other outcomes:
measure: The proportion of patients vomiting their medication within 1 hour of administration
timeFrame: 1 h
measure: The proportion of patients vomiting any of their PQ doses during the supervised course
timeFrame: 7 - 14days
measure: The proportion of adverse events and serious adverse events
timeFrame: 6 month
measure: The incidence risk of severe anaemia (Hb<7g/dl) and/or the risk for blood transfusion
timeFrame: 6 month
measure: Risk of greater than 25% fall in haemoglobin on any day of treatment
timeFrame: 7-14days
measure: The incidence risk of an acute drop in Hb of >5g/dl during PQ treatment
timeFrame: 7-14days
Locations:
city: Malakheti
country: Nepal
facility: Malakheti Hospital
city: Tikapur
country: Nepal
facility: Tikapur Hospital
Study officials:
affiliation: Menzies School of Health Research
name: Kamala Ley-Thriemer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: