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

Malaria Clinical Trial

— PRIMA  

Official title:

Reducing the Risk of P. Vivax After Falciparum Infections in Co-endemic Areas - a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03916003
• Other study ID #: 19-3288
• Status: Completed
• Phase: Phase 4
• Start date: August 18, 2019
• Est. completion date: July 30, 2022

Study information

• Verified date: November 2023
• Source: Menzies School of Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: July 30, 2022
• Est. primary completion date: May 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

Inclusion Criteria:

• P. falciparum mono-infection
• Fever (axillary temperature =37.5°C) 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 ß-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

Related Conditions & MeSH terms

• Falciparum Malaria
• Malaria
• Malaria, Falciparum
• Malaria, Vivax
• Vivax Malaria

Intervention

Drug:
• primaquine
Primaquine regimen over 7 days (1.0 mg/kg/day for 7 days)

Locations

Country	Name	City	State
Bangladesh	Icddrb	Upazila
Ethiopia	Arba Minch University	Arba Minch
Indonesia	Puskesmas Mangili	Dusun Tenggara

Sponsors (5)

Lead Sponsor	Collaborator
Menzies School of Health Research	Addis Ababa University, Arba Minch University, International Centre for Diarrhoeal Disease Research, Bangladesh, Tribhuvan University, Nepal

Countries where clinical trial is conducted

Bangladesh,  Ethiopia,  Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence risk of any P. vivax parasitaemia at day 63	The incidence risk of any P. vivax parasitaemia at day 63	63 days
Secondary	Incidence risk of symptomatic P. vivax parasitaemia at day 63	incidence risk of symptomatic P. vivax parasitaemia at day 63	63 days
Secondary	Incidence risk of all any P. vivax parasitaemia at day 28 and 42	Incidence risk of all any P. vivax parasitaemia at day 28 and 42	28 and 42 days
Secondary	Incidence risk of any P. falciparum malaria at day 28, 42 and 63	incidence risk of any P. falciparum malaria at day 28, 42 and 63	28/42/63 days
Secondary	proportion of patients vomiting their medication within 1 hour of administration	proportion of patients vomiting their medication on the day of enrollment within 1 hour of administration	1 hour
Secondary	proportion of patients vomiting any of their PQ doses within 1 hour of administration	proportion of patients vomiting any of their PQ doses within 1 hour of administration	7 days
Secondary	proportion of adverse events and serious adverse events	proportion of adverse events and serious adverse events	63 days
Secondary	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	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	7 days
Secondary	• The incidence risk of =25% fall in haemoglobin since baseline with and without hemoglobinuria at day 3 and day 7	• The incidence risk of =25% fall in haemoglobin since baseline with and without hemoglobinuria at day 3 and day 7	7 days
Secondary	The incidence risk of =25% fall in haemoglobin to under 7g/dl with and without hemoglobinuria at day 3 and day 7	The incidence risk of =25% fall in haemoglobin to under 7g/dl with and without hemoglobinuria at day 3 and day 7	day 7
Secondary	Incidence risk of P. falciparum gametocytaemia between day 7 and 63	Incidence risk of P. falciparum gametocytaemia between day 7 and 63	63 days
Secondary	Parasite clearance on day 1, 2 and 3	Parasite clearance on day 1, 2 and 3	3 days
Secondary	Fever clearance on day 1, 2 and 3	Fever clearance on day 1, 2 and 3	3 days