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

NCT ID: NCT03916003

Last Updated: 2023-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-18
• Study Completion Date: 2022-07-30

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.

Conditions

Malaria; Vivax Malaria; Falciparum Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PQ7

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

Group Type: EXPERIMENTAL

primaquine

Intervention Type: DRUG

Primaquine regimen over 7 days (1.0 mg/kg/day for 7 days)

standard care

As per national guidelines for P. falciparum treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

primaquine

Primaquine regimen over 7 days (1.0 mg/kg/day for 7 days)

Intervention Type: DRUG

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

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role: collaborator

Tribhuvan University, Nepal

OTHER

Sponsor Role: collaborator

Arba Minch University

OTHER

Sponsor Role: collaborator

Addis Ababa University

OTHER

Sponsor Role: collaborator

Menzies School of Health Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kamala Thriemer, MD

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Locations

Icddrb

Upazila, , Bangladesh

Arba Minch University

Arba Minch, , Ethiopia

Puskesmas Mangili

Dusun Tenggara, , Indonesia

Countries

Bangladesh; Ethiopia; Indonesia

References

Thriemer K, Degaga TS, Christian M, Alam MS, Rajasekhar M, Ley B, Hossain MS, Kibria MG, Tego TT, Abate DT, Weston S, Mnjala H, Rumaseb A, Satyagraha AW, Sadhewa A, Panggalo LV, Ekawati LL, Lee G, Anose RT, Kiros FG, Simpson JA, Karahalios A, Woyessa A, Baird JK, Sutanto I, Hailu A, Price RN. Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial. Lancet. 2023 Dec 2;402(10417):2101-2110. doi: 10.1016/S0140-6736(23)01553-2. Epub 2023 Nov 15.

Reference Type: DERIVED

PMID: 37979594 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35585641 (View on PubMed)

Other Identifiers

19-3288

Identifier Type: -

Identifier Source: org_study_id