Radical Cure (RC) With Tafenoquine or Primaquine After Semi-quantitative G6PD Testing: A Feasibility Study in Peru

NCT ID: NCT05361486

Last Updated: 2023-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-08-28

Study Completion Date

2024-10-31

Brief Summary

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The goal of this study is to evaluate the operational feasibility of using a new treatment algorithm for Malaria Vivax in Peru.

The implementation package includes the following interventions:

* A revised vivax treatment algorithm that incorporates new Radical Cure tools (G6PD test + Tafenoquine or Primaquine)
* The training of Health Care Providers ( HCPs) in the revised algorithm and the use of the new RC tools
* Patient counselling
* A follow-up visit at Day 3 \[+2 days\] for patients after treatment start
* Accompanying supporting measures: job aids, strengthening of supervision and PV processes

Detailed Description

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The goal of this study is to evaluate the operational feasibility of providing Tafenoquine and Primaquine after semi-quantitative G6PD testing at different levels of the health services, in order to inform potential policy change, malaria strategy, and introduction planning.

This implementation research study will be carried out in Peru among 40 Health Care Providers ( HCPs) each treating a minimum of 15 patients with P. vivax malaria. The study will be conducted in Loreto Region (Loreto, Maynas and Ramon Castilla provinces), an area which is endemic for P. vivax.

A total of 30 health facilities will be included: 6 in the first phase and 12 will be added in the second phase. An additional 12 health facilities have been selected as backup in case the malaria case load is low, and this is needed in order to meet the sample size.

All relevant HCP working in study facilities will be trained on the relevant aspects of performing the G6PD testing, interpreting its result, evaluating patient's eligibility for Radical Cure and choosing the appropriate treatment as per their role accordingly.

HCP knowledge and skills regarding semi-quantitative G6PD testing and RC treatment will be assessed through standardized competency assessment (including self-assessments).

Adherence to the revised algorithm will be evaluated as follows. At each HF included in the study, the ideal patient case management cascade will be defined a priori. Individual HCP adherence to each step of the case management will be assessed against this cascade. By indexing each step in the patient care cascade to a specific HCP, the study will be able to consider feasibility at multiple levels, analysing adherence to specific steps of the case management algorithm.

A specific process will be put in place for patient counselling and standard tools such as a counselling checklist will be developed to assist HCPs. In addition, patient materials will be developed which will give explanations on the new Radical Cure tools, emphasize the need to come for a follow-up visit and outline the potential side effects that can be elicited by 8-AQ. Patients will be instructed to come back or call the facilities in case they experience those events.

The study will be carried out in following phases:

1. A formative research and baseline phase ( approx. 3 months) : this phase is meant to collect baseline information from the selected study facilities prior to introduction of the implementation package. This phase will also be important to field-test and validate study tools, such as the training material and documents and data collection tools (e.g. qualitative research questionnaires and interview guides). Finally, during this formative research phase, the supervision processes and tools will be revised.
2. A higher-level facilities phase ( approx. 8 months) : in this phase the implementation package will only be rolled out in selected higher-level facilities.

An interim analysis will be conducted prior to rolling out the implementation package to lower-level facilities. The data cut-off point for this interim analysis will be once 50 patients have been treated with the revised algorithm. During this interim analysis, enrolment in Higher-level HF will continue.
3. An All-level facilities phase ( approx.14 months) : in this phase the implementation package will be rolled out to the lower-level facilities.

Final analysis will be performed at study end and results will be shared with the Peru National Malaria Control Program (NMCP) to make informed decisions on revisions to national malaria treatment policies.

The study aims to achieve the following specific objectives:

1. Assess HCP adherence to a revised case management algorithm for vivax malaria that involves providing RC treatment after semi-quantitative G6PD testing and a follow-up visit. This will be assessed at the provider, patient, and health facility (HF) level.
2. Determine the ability of HCP to safely implement RC treatment after semi-quantitative G6PD testing
3. Evaluate the quality and effectiveness of training and supervision strategies to support the implementation of semi-quantitative G6PD testing before RC treatment
4. Explore barriers and facilitators at the patient, provider, and facility level that mediate effective use of RC treatment with semi-quantitative G6PD testing. 5. Determine the costs associated with introducing semi-quantitative G6PD testing before RC treatment as part of routine care

Conditions

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Malaria, Vivax

Keywords

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Feasibility study, Tafenoquine, G6PD Testing

Study Design

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Observational Model Type

ECOLOGIC_OR_COMMUNITY

Study Time Perspective

PROSPECTIVE

Study Groups

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Health Care Provider managing vivax patients in study facilities

All HCPs working in the selected facilities who are involved in the management of vivax patients will be approached to participate in the study.

Training on revised algorithm

Intervention Type OTHER

relevant HCP working in study facilities will be trained on the relevant aspects of performing the G6PD testing, interpreting its result, evaluating patient's eligibility for RC and choosing the appropriate treatment as per their role accordingly

Enhancing Pharmacovigilance

Intervention Type OTHER

Refresher training on PV reporting in the selected facilities. National PV forms will be reviewed and if required, modified in consultation with the national PV system.

Supervision of malaria services in selected facilities.

Intervention Type OTHER

Supervisors in target regions will be trained as for the HCPs.

Patients with confirmation of vivax, attending one of the study facilities

All patients aged 6 months onward, who have a confirmed P. vivax infection and who are in a study HF will be approached to participate in the study. This includes pregnant and lactating women, who have a contra-indication to both PQ and TQ, but for whom correct case management will be evaluated as part of the primary endpoints.

G6PD testing

Intervention Type DIAGNOSTIC_TEST

G6PD test after Malaria Vivax diagnosis

Tafenoquine

Intervention Type DRUG

300 mg (2x150mg tablets) tafenoquine

Primaquine

Intervention Type DRUG

0.5mg/kg/7 days

Follow Up Visit at Day 3 [+2 days] after treatment start

Intervention Type OTHER

It will be checked if all patients have a Follow Up Visit at Day 3 \[+2 days\] after treatment start

Interventions

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Training on revised algorithm

relevant HCP working in study facilities will be trained on the relevant aspects of performing the G6PD testing, interpreting its result, evaluating patient's eligibility for RC and choosing the appropriate treatment as per their role accordingly

Intervention Type OTHER

Enhancing Pharmacovigilance

Refresher training on PV reporting in the selected facilities. National PV forms will be reviewed and if required, modified in consultation with the national PV system.

Intervention Type OTHER

Supervision of malaria services in selected facilities.

Supervisors in target regions will be trained as for the HCPs.

Intervention Type OTHER

G6PD testing

G6PD test after Malaria Vivax diagnosis

Intervention Type DIAGNOSTIC_TEST

Tafenoquine

300 mg (2x150mg tablets) tafenoquine

Intervention Type DRUG

Primaquine

0.5mg/kg/7 days

Intervention Type DRUG

Follow Up Visit at Day 3 [+2 days] after treatment start

It will be checked if all patients have a Follow Up Visit at Day 3 \[+2 days\] after treatment start

Intervention Type OTHER

Other Intervention Names

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Kozenis

Eligibility Criteria

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Inclusion Criteria

• All HCPs working in the selected facilities who are involved in the management of vivax patients.


* All patients aged 6 months onward, who have a confirmed P. vivax infection and who are treated in a study Health Facilities
* Pregnant and lactating women, who have a contra-indication to both Primaquine and Tafenoquine, but for whom correct case management will be evaluated as part of the primary endpoints.
* Patients providing informed consent and/or informed assent

Exclusion Criteria

• Patients with signs of severe infection
Minimum Eligible Age

6 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Universidad Peruana Cayetano Heredia

OTHER

Sponsor Role collaborator

UNITAID

OTHER

Sponsor Role collaborator

ICON plc

INDUSTRY

Sponsor Role collaborator

Medicines for Malaria Venture

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elmer Alejandro Llanos Cuentas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad Peruana Cayetano Heredia (UPCH)

Locations

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Nauta Nucleo- Base

Nauta, Loreto, Peru

Site Status RECRUITING

Countries

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Peru

Central Contacts

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Thy Do, PhD

Role: CONTACT

Phone: +4179 515 94 05

Email: [email protected]

Elisa Vidal, PhD

Role: CONTACT

Phone: +51984739393

Email: [email protected]

Facility Contacts

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Veronica Soto, MD

Role: primary

Ivan Condori, MS

Role: backup

References

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Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, Krudsood S, Gupta SK, Kochar SK, Arthur P, Chuenchom N, Mohrle JJ, Duparc S, Ugwuegbulam C, Kleim JP, Carter N, Green JA, Kellam L. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet. 2014 Mar 22;383(9922):1049-58. doi: 10.1016/S0140-6736(13)62568-4. Epub 2013 Dec 19.

Reference Type BACKGROUND
PMID: 24360369 (View on PubMed)

Anderle A, Bancone G, Domingo GJ, Gerth-Guyette E, Pal S, Satyagraha AW. Point-of-Care Testing for G6PD Deficiency: Opportunities for Screening. Int J Neonatal Screen. 2018;4(4):34. doi: 10.3390/ijns4040034. Epub 2018 Nov 19.

Reference Type BACKGROUND
PMID: 31709308 (View on PubMed)

Chu CS, Bancone G, Kelley M, Advani N, Domingo GJ, Cutiongo-de la Paz EM, van der Merwe N, Cohen J, Gerth-Guyette E. Optimizing G6PD testing for Plasmodium vivax case management and beyond: why sex, counseling, and community engagement matter. Wellcome Open Res. 2020 Aug 25;5:21. doi: 10.12688/wellcomeopenres.15700.2. eCollection 2020.

Reference Type BACKGROUND
PMID: 32766454 (View on PubMed)

Commons RJ, Simpson JA, Watson J, White NJ, Price RN. Estimating the Proportion of Plasmodium vivax Recurrences Caused by Relapse: A Systematic Review and Meta-Analysis. Am J Trop Med Hyg. 2020 Sep;103(3):1094-1099. doi: 10.4269/ajtmh.20-0186.

Reference Type BACKGROUND
PMID: 32524950 (View on PubMed)

Domingo GJ, Advani N, Satyagraha AW, Sibley CH, Rowley E, Kalnoky M, Cohen J, Parker M, Kelley M. Addressing the gender-knowledge gap in glucose-6-phosphate dehydrogenase deficiency: challenges and opportunities. Int Health. 2019 Jan 1;11(1):7-14. doi: 10.1093/inthealth/ihy060.

Reference Type BACKGROUND
PMID: 30184203 (View on PubMed)

Douglas NM, Poespoprodjo JR, Patriani D, Malloy MJ, Kenangalem E, Sugiarto P, Simpson JA, Soenarto Y, Anstey NM, Price RN. Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study. PLoS Med. 2017 Aug 29;14(8):e1002379. doi: 10.1371/journal.pmed.1002379. eCollection 2017 Aug.

Reference Type BACKGROUND
PMID: 28850568 (View on PubMed)

Edwards SJ, Braunholtz DA, Lilford RJ, Stevens AJ. Ethical issues in the design and conduct of cluster randomised controlled trials. BMJ. 1999 May 22;318(7195):1407-9. doi: 10.1136/bmj.318.7195.1407. No abstract available.

Reference Type BACKGROUND
PMID: 10334756 (View on PubMed)

Other Identifiers

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MMV_TQ_21_01

Identifier Type: -

Identifier Source: org_study_id