Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202110493521020 Date of Registration: 19/10/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Assessing new Paediatric tablet of Primaquine as radical cure in Ethiopia
Official scientific title Developing Paediatric Primaquine – Assessing new paediatric tablets of primaquine as radical cure in Ethiopia
Brief summary describing the background and objectives of the trial In Ethiopia, P. falciparum and P. vivax are co-endemic in almost all malarious areas and their proportion seem unchanged over the years. Plasmodium vivax (~40%) pauses a significant burden in the country. Moreover, among , 409,000 malaria deaths that occurred globally,67% were children under the age of 5 years. Vivax malaria disproportionately affects young children, peaking between 2 to 6 years. Ethiopia achieved the 2020 global target; reducing the incidence of malaria by 40% in 2019. Encouraged by the over two decades of success, the National Malaria Elimination Program (NMEP) has embarked on an elimination program. This move for the end game fundamentally rest on the success in interrupting the cycle of plasmodium transmission between the Anopheline mosquito vectors and humans. Thus, prompt and effective treatment involving radical cure is one of the cornerstones of the armaments currently available. Transmission blocking is the key drive in adopting the administration of the gametocidal drug primaquine (PQ) in combination with first line-regimens; single- and 14-days low dose (0.25mg/Kg) with ACT and CQ to treat uncomplicated falciparum and vivax malaria respectively in Ethiopia. Yet, there are formidable challenges that countries including Ethiopia face as they deploy PQ. These include: (i) currently available PQ is costly, thus self-sustained elimination may be challenging (ii) insufficient tablet strengths to cover all patients, (iii) no pediatric formulations, (iv) no user-friendly blister packs, and (v) no PQ regimen that avoids Glucose-6-Phosphate-Dehydroginase deficiency (G6PDd) testing. These challenges need to be overcome for malaria elimination to progress. Therefore, this study aims to conduct a clinical trial to evaluate the acceptability, pharmacokinetics, efficacy and safety for radical cure of uncomplicated vivax malaria of new generic primaquine tablets in children and adolescents.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) DPP APPE
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/08/2024
Actual trial start date 01/09/2024
Anticipated date of last follow up 31/05/2025
Actual Last follow-up date 30/06/2025
Anticipated target sample size (number of participants) 120
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Artemether lumefantrine or Chloroquine and Primaquine ABC in patient with normal G6PD Artemether lumefantrine determined by body weight Chloroquine 25mg/kg divided doses over 3 days Primaquine A, B and C 0.25 mg base/kg/day over 14 days. 14 days Artemether lumefantrine or Chloroquine and Primaquine A (D0-D5), Primaquine B (D6-D9), Primaquine C (D10-D13) Artemether lumefantrine will be used for mix infection Chloroquine will be used for P. vivax mono-infected Primaquine blister pack will contain three PQ tablets: two flavoured and one standard bitter tablet. Tablet sequences will vary (ABC, BAC or CAB) but the sequence will only be known to the blister pack manufacturer. 40
Experimental Group Artemether lumefantrine or Chloroquine and Primaquine BAC in patient with normal G6PD Artemether lumefantrine determined by body weight Chloroquine 25mg/kg divided doses over 3 days Primaquine A, B and C 0.25 mg base/kg/day over 14 days. 14 days Artemether lumefantrine or Chloroquine and Primaquine B (Day 0-Day 5), Primaquine A (Day 6-Day 9), Primaquine C (Day 10-Day 13) Artemether lumefantrine will be used for mix infection Chloroquine will be used for P. vivax mono-infected Primaquine blister pack will contain three PQ tablets: two flavoured and one standard bitter tablet. Tablet sequences will vary (ABC, BAC or CAB) but the sequence will only be known to the blister pack manufacturer. 40
Experimental Group Artemether lumefantrine or Chloroquine and Primaquine CAB in patient with normal G6PD Artemether lumefantrine determined by body weight Chloroquine 25mg/kg divided doses over 3 days Primaquine A, B and C 0.25 mg base/kg/day over 14 days. 14 days Artemether lumefantrine or Chloroquine and Primaquine C (Day 0-Day 5), Primaquine A (Day 6-Day 9), Primaquine B (Day 10-Day 13) Artemether lumefantrine will be used for mix infection Chloroquine will be used for P. vivax mono-infected Primaquine blister pack will contain three PQ tablets: two flavoured and one standard bitter tablet. Tablet sequences will vary (ABC, BAC or CAB) but the sequence will only be known to the blister pack manufacturer. 40
Control Group Artemether lumefantrine or Chloroquine and Primaquine for G6PD deficiency group Artemether lumefantrine determined by body weight Chloroquine 25mg/kg divided doses over 3 days The dose of weekly primaquine will be based on a target dose of 0.5 mg/kg/week x 7 doses. 7 weeks Artemether lumefantrine or Chloroquine and Primaquine Artemether lumefantrine will be used for mix infection Chloroquine will be used for P. vivax mono-infected 5 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Those living within 20 km of the catchment of the health facility with a traceable address or phone contact number 2. Parent/legal guardian is willing to comply with the study protocol and visit schedule, including attendance in person for all necessary visits at study site 3. Able to give assent for patients aged 12 – 16 years and Parental/legal guardian informed written consent 4. Age ≥ 6 months and < 16 years at the time of consent 5. Weight ≥ 5.0 kg 6. Slide-confirmed P. vivax mono- or mixed infections 7. Axillary temperature ≥ 37.5º C or history of fever during the previous 10 days 8 Ability to swallow oral medication 1. General danger signs or symptoms of severe malaria 2.Haemoglobin (Hb) <5 g/dL 3. Presence of febrile conditions caused by diseases other than malaria (e.g. measles, acute lower respiratory tract infection, COVID-19, severe diarrhoea with dehydration) 4. COVID-19 positive by a lateral flow antigen test (Follow the Ethiopian Public Health Institute's guidelines and recommendations for testing. 5. Serious or chronic medical condition (e.g. cardiac, renal, hepatic diseases, sickle cell disease) 6. History of hypersensitivity to study or rescue medication in this study 7. Taking regular medication which may interfere with antimalarial PK or efficacy 8. Severe malnutrition in a child aged between 6-59 months as defined by the presence of symmetrical oedema involving at least the feet or a mid-upper arm circumference < 115 mm 9. Known pregnancy or UPT positive at the screening visit Adolescent: 13 Year-18 Year,Child: 6 Year-12 Year,Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 6 Month(s) 15 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/09/2021 AHRI ALERT
Ethics Committee Address
Street address City Postal code Country
Jimma Road, ALERT Compound Addis Ababa 1005 Ethiopia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/12/2021 National Research Ethics Review committee
Ethics Committee Address
Street address City Postal code Country
Arada Addis Ababa 2490 Ethiopia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 05/06/2024 Ethiopian Food and Drug Authority
Ethics Committee Address
Street address City Postal code Country
Africa Avenue, near Wolosefer, Kirkos sub city Addis Ababa 5681 Ethiopia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Assess the antirelapse efficacy and safety of daily or weekly primaquine using new generic formulations in children aged 6m to < 16 years in Ethiopia D0, D1, D2, D3, D7, D14, D21, D28, D35, D42, M2, M3, M4, M5, M6
Secondary Outcome 1. Determine the haematological response of daily or weekly primaquine using new generic formulations in children aged 6m to < 16 years 2. Evaluate the acceptability of new generic PQ regimes in vivax malaria patients 6m to < 16 years 3. Characterise PQ and carboxyPQ disposition 4. Assess CQ exposure 5. Characterise cytochrome P450 2D6 activity 6. Characterise host genetics for inherited blood disorders 7. Determine Day 28 parasitological and clinical efficacy 8. Determine asexual parasite and gametocyte dynamics 9. Determine parasite genetics 10 .Assess socioeconomic factors related to malaria D0, D1, D2, D3, D7,D14, D28, D42, M2,M3, M4, M5, M6
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Armauer Hansen Research InstituteAHRI Jimma Road, ALERT Compound Addis Ababa 1005 Ethiopia
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership EDCTP. Grant code RIA2019PD2893 2509 AA The Hague, The Netherlands Hague 93015 250 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor The Masters and Scholars of the University of Oxford University of Oxford University Offices, Wellington Square Oxford OX1 2JD United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Mahidol Oxford Tropical Medicine Clinical Research unit MORU 420/6 Rajvithi road,Rajthevee Bangkok 10400 Thailand
Ministry of Health Ethiopia 1234 Sudan Street Addis Ababa 122326 Ethiopia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Endalamaw Gadisa endalamaw.gadisa@ahri.gov.et +251911868827 Jimma Road,ALERT compound
City Postal code Country Position/Affiliation
Addis Ababa 1005 Ethiopia Armauer Hansen Research Institute
Role Name Email Phone Street address
Principal Investigator Bob Taylor bob@tropmedres.ac 6622036333 420/6 Rajvithi road, Rajthevee
City Postal code Country Position/Affiliation
Bangkok 10400 Thailand Mahidol Oxford Tropical Medicine Clinical Research unit MORU
Role Name Email Phone Street address
Public Enquiries Demekech Damtie demekech@gmail.com +251918776730 Jimma Road ALERT compound
City Postal code Country Position/Affiliation
Addis Ababa 1005 Ethiopia Secretariat of the Ethics Review Committee
Role Name Email Phone Street address
Scientific Enquiries Endalamaw Gadisa endalamaw.gadisa@ahri.gov.et +251911868827 Jimma Road,ALERT compound
City Postal code Country Position/Affiliation
Addis Ababa 1005 Ethiopia Armauer Hansen Research Institute
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Plan to share the IPD at the end of the study Informed Consent Form,Statistical Analysis Plan,Study Protocol At the end of the study The data generated in this study belongs to the study group as a whole. The final database will be shared amongst the site PI and key members of the research team. The database may be shared with researchers not directly involved in this study but only after the main paper has been published and in accordance with AHRI and MORU guidelines on data sharing. The database will only be shared if future publications are not compromised. The criteria for authorship will be consistent with the international guidelines. At the end of the study, the results will be shared with the local community
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information