Clinical trial NCT05753150: Operational Feasibility of Appropriate Plasmodium Vivax Radical Cure After G6PD Testing in Thailand
Official title: Operational Feasibility of Appropriate Plasmodium Vivax Radical Cure With Tafenoquine or Primaquine After Quantitative G6PD Testing in Thailand
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Malaria, Vivax
G6PD Deficiency
Keywords: Tafenoquine
Primaquine
G6PD testing
Operational study
Thailand
Lead sponsor: Ministry of Health, Thailand
Sponsor class: OTHER_GOV
Collaborators: name: Medicines for Malaria Venture
First posted: 2023-03-03
Enrollment: 187
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will be conducted at hospitals and malaria clinics in the provinces of Yala and Mae Hong Son in Thailand.

Brief summary: The purpose of this prospective, observational study is to assess the operational feasibility of appropriate radical cure treatment for P. vivax malaria with tafenoquine or primaquine, in patients 16 year and older, after G6PD testing in Thailand. The study will be implemented in a phased manner, in the provinces of Yala and Mae Hong Son. The first phase will be at higher level health facilities (hospitals). An interim analysis will be conducted after 40 patients are enrolled in the study in order to decide whether the study could be extended to lower level HFs. If approved by the Independent Study Oversight Committee, the study will be implemented in lower level HFs (malaria clinics).Higher level HFs will continue to include patients in the study during this 2nd phase.Written informed consent / assent is required from all patients /guardians in the case of minors.

Detailed description: This is a prospective, observational, multi-center, longitudinal study to be conducted in Yala province and Mae Hong Son province in patients with P. vivax malaria.

Since 2020, quantitative G6PD testing has been available for routine use prior to providing PQ radical therapy at district hospitals and malaria clinics in the study provinces, in line with the national guidelines.

Before study start, the relevant staff at all participating sites will be re-trained on the quantitative G6PD test procedure and the radical cure treatment algorithm by the Division of Vector Borne Diseases (DVBD). Standard operating procedures (SOP) for identification of patients with suspected AHA and guidance for initial management and transfer to a referral hospital will be provided.

G6PD tests and TQ will be supplied to Health Facilities (HFs) by the DVBD using the usual supply route for drugs and diagnostics. PQ and other anti-malarial drugs are already available in Thailand.

Within the study period, investigators will prospectively enroll all patients meeting the selection criteria.

Each patient will have to sign an Informed Consent Form (ICF) indicating their consent for participation in the study by being considered for treatment with TQ provided that they have the appropriate G6PD enzyme activity (or treated with PQ, according to the current practice, otherwise) and permitting investigators to use their unidentified data for analysis purposes. Assent from patients \<18 years of age, and the parent's or legal guardian's written informed consent must be obtained.

This study will not change the patient/physician relationship, nor influence the investigator's drug prescription or therapeutic management of the patient other than what is specified regarding the algorithm for radical cure treatment of P. vivax malaria with TQ and PQ.

As part of local practice in Yala province and Mae Hong Son province, patients treated for P. vivax infection are asked to return for a follow-up visit on Day 5 (+/- 1 day). This is in addition to the national policy of the first scheduled follow-up visit on Day 14 (+2/- 1 day) for vivax malaria patients. Patient data will be collected by the investigators on each patient visit.

Any suspected case of AHA will be transferred to Yala Referral Hospital, the regional hospital with one board-certified haematologist or to the Mae Hong Son Provincial Hospital. Both hospitals have full services of blood transfusion, renal dialysis, and other life-saving procedures, for further investigation and treatment.

As some patients may not return for the follow-up visits and might develop drug-induced AHA, the study staff at the referral hospitals will regularly screen hospital admission records for malaria patients participating in the study presenting signs of AHA, diagnosed with renal failure, and/or receiving blood transfusion.

The study will be conducted in 2 phases:

* 1st phase (for about 3 months): the study will be implemented in higher level HFs (hospitals). An interim analysis will be conducted after 40 patients (≥16 years old) with P. vivax are enrolled in the study in order to decide whether the study could be extended to lower level HFs. The decision will be made by an Independent Study Oversight Committee (ISOC).
* 2nd phase (approximately 2 months): if approved by the ISOC, the study will be implemented in lower level HFs (malaria clinics).

Higher level HFs will continue to include patients in the study during this 2nd phase.

Final results will be reviewed by the ISOC. It is anticipated that it will take a total of about 11-12 months to complete data collection at the target hospitals and malaria clinics.

Eligibility criteria: Inclusion Criteria:

* Thai patient aged ≥16 years at enrolment
* Diagnosed with a mono-species, uncomplicated P. vivax malaria that is parasitologically confirmed through standardized Giemsa microscopy.
* Weighs \>35 kg
* Haemoglobin level must be \>7gm%
* Less than 24h away from emergency care

Exclusion Criteria:

* Participating in a clinical trial
* Diabetic patients who are (1) being treated with metformin (because of possible increase in the risk of lactic acidosis due to metformin when administered in combination with tafenoquine) (2) G6PD-deficient and being treated with sulfonylureas e.g. Glucotrol, Glynase, Metaglip and Micronase (because of the increased risk of haemolysis in this population).
* Pregnant/lactating women, women with suspected pregnancy.1
* Cases of severe/ complicated malaria

Primary outcomes:
measure: Appropriate use of TQ based on G6PD activity
timeFrame: 8 months
Secondary outcomes:
measure: Appropriate use of PQ based on G6PD activity
timeFrame: 8 months
measure: Appropriate application of treatment algorithm
timeFrame: 8 months
measure: Reported drug-induced AHA.
timeFrame: 8 months
Other outcomes:
Locations:
city: Mae Sariang
country: Thailand
facility: District Hospital
state: Mae Hong Son
city: Mae Sariang
country: Thailand
facility: Malaria Clinic
state: Mae Hong Son
city: Sop Moei
country: Thailand
facility: District Hospital
state: Mae Hong Son
city: Bannang Sata
country: Thailand
facility: District Hospital
state: Yala
city: Bannang Sata
country: Thailand
facility: Malaria Clinic
state: Yala
city: Kabang
country: Thailand
facility: District Hospital
state: Yala
city: Mueang
country: Thailand
facility: Malaria Clinic
state: Yala
city: Than To
country: Thailand
facility: District Hospital
state: Yala
city: Than To
country: Thailand
facility: Malaria Clinic
state: Yala
Study officials:
affiliation: Director, Dept. Vector Borne Diseases (DVBD)
name: Chantana Padungtod, M.D., DrPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Director, ODPC Reg. No. 1
name: Saowanee Viboonsanti, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Director, ODPC Reg. No. 12
name: Chalermpol Chalermpol, M.D.
role: PRINCIPAL_INVESTIGATOR
References: