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.: PACTR201611001859416 Date of Approval: 11/11/2016
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Addition of low dose primaquine to artemether-lumefantrine for the treatment of uncomplicated malaria
Official scientific title A randomised controlled trial to investigate the efficacy, safety and tolerability of adding a single low primaquine dose to artemether-lumefantrine for the treatment of symptomatic uncomplicated Plasmodium falciparum malaria
Brief summary describing the background and objectives of the trial Since 2012 the WHO has recommended administration of a single low dose of primaquine (0.25 mg/kg) to reduce onward transmission in low transmission areas. Available data suggest that this will not cause haemolysis in G6PD-deficient individuals. Although most African malaria eliminating countries have expressed an interest in adopting a primaquine policy for transmission blocking, they have raised concerns over the safety of primaquine in G6PD-deficient individuals and other vulnerable populations including young children and patients with co-morbidities such as HIV and TB. The investigators of this study have been asked by the South African National Malaria Control Programme to evaluate obstacles cited as reasons for not yet implementing a single low dose primaquine policy in South Africa. This study will generate data on efficacy to reduce gametocyte carriage, as well as safety and tolerability of adding a single low primaquine dose to artemether-lumefantrine treatment in 140 symptomatic uncomplicated malaria patients. A number of factors may shift the risk:benefit profile of primaquine, including CYP2D6 genotype and G6PD status (only expected at higher primaquine doses), so describing the prevalence of these in the target population screened will provide useful information to inform larger-scale deployment of primaquine. The primary objectives are to evaluate the efficacy of artemether-lumefantrine alone versus adding a single 0.25 mg/kg primaquine dose after artemether-lumefantrine treatment in patients with uncomplicated falciparum malaria, as measured by changes in gametocyte prevalence on days 7 and 14 using RT-PCR and to compare the change in mean haemoglobin associated with artemether-lumefantrine alone versus adding a single 0.25 mg/kg primaquine dose after artemether-lumefantrine treatment in patients with uncomplicated falciparum malaria, as measured by HemoCue® on day 3 (before primaquine dose) versus day 7
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PRIM01
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 18/11/2016
Actual trial start date 12/12/2016
Anticipated date of last follow up 01/06/2017
Actual Last follow-up date 01/08/2019
Anticipated target sample size (number of participants) 140
Actual target sample size (number of participants) 140
Recruitment status Completed
Publication URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592007/
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
Parallel: different groups receive different interventions at same time during study Randomised Random number generation, stratified by clinic, prepared by an independent statistician using a valid system Sealed opaque enveloped Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Randomised Random number generation, stratified by clinic, prepared by an independent statistician using a valid system Sealed opaque enveloped Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Randomised Random number generation, stratified by clinic, prepared by an independent statistician using a valid system Sealed opaque enveloped Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Standard of care (artemether-lumefantrine) According to standard of care According to standard of care Tablets 70 Active-Treatment of Control Group
Experimental Group Primaquine plus standard of care (artemether-lumefantrine) 0.25mg/kg primquine according to WHO dosing guide with standard of care for artemether-lumefantrine Single dose primaquine and artemether-lumefantrine according to standard of care Primaquine 15mg tablets and artemether-lumefantrine according to standard of care 70 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Plasmodium falciparum positive by RDT Age > 2 years Weight over 10 kg Prescribed artemether-lumefantrine according to standard practice Informed consent (by legally acceptable representative if under 18 years of age) Assent in children aged 7 and above Intention to remain in the study area for the duration of the follow-up period Evidence of severe illness/ danger signs Known allergy to study medications Medical history of haemolysis, rheumatoid arthritis, lupus erythematosus or cardiac disease In patients receiving concurrently other drugs that are cause hemolysis, bone marrow suppression or QTc interval prolongation Hb < 7 g/dL A decrease in Hb of > 2 g/dL between day 0 and day 3 prior to primaquine dose Currently menstruating Pregnant or breastfeeding History of any antimalarials (including primaquine) taken within the last 4 weeks Blood transfusion within the last 90 days 2 Year(s) 100 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 21/09/2016 University of Cape Town Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Old Main Building, Groote Schuur Hospital, Observatory Cape Town 7295 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Changes in gametocyte prevalence on days 7 and 14 using RT-PCR Day 7 Day 14
Primary Outcome Change in mean haemoglobin (Hb) as measured by HemoCue on day 3 Day 3
Secondary Outcome Prevalence of severe anaemia, haemoglobinuria and adverse events Day 3 Day 7 Day 14 Day 28 Day 42
Secondary Outcome Efficacy of artemether-lumefantrine by asexual parasite recrudescence and reinfection rates over 42 days Day 42
Secondary Outcome Prevalence of molecular markers associated with artemesinin and lumefantrine resistance Day 3 Day 7 Day 14 Day 21 Day 28 Day 42
Secondary Outcome Prevalence of G6PD deficiency using CareStart G6PD RDT Day 0
Secondary Outcome Sensitivity and specificity of CareStart G6PD RDT Day 0
Secondary Outcome Day 7 blood concentration of lumefantrine Day 7
Secondary Outcome Prevalence of G6PD mutant variants Day 0
Secondary Outcome Prevalence of CYP2D6 mutant alleles Day 0
Secondary Outcome Sensitivity and specificity of LAMP compared to PCR for detecting falciparum malaria Day 0 Day 3 Day 7 Day 14 Day 28 Day 42
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Komatipoort Clinic Komatipoort South Africa
Madimbo clinic Madimbo South Africa
Naas Clinic Naas South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
South African Medical Research Council Francie van Zijl Drive Cape Town 7505 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Cape Town Clinical Research Centre, OMB Groote Schuur Hospital, Observatory Cape Town 7295 South Africa University
COLLABORATORS
Name Street address City Postal code Country
University of Cape Town K47.22 OMB, Groote Schuur Hospital, Observatory Cape Town 7295 South Africa
National Institute of Communicable Diseases 1 Modderfontein Road, Sandringham Johannesburg 2131 South Africa
University of Witwatersrand 1 Jan Smuts Avenue Braamfontein 2000 South Africa
University of Pretoria cnr Lynnwood Road and Roper Street Pretoria South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Karen Barnes karen.barnes@uct.ac.za +27 406 6008 K47.22 OMB, Groote Schuur Hospital, Observatory
City Postal code Country Position/Affiliation
Cape Town 7295 South Africa Acting Head of Division of Clinical Pharmacology
Role Name Email Phone Street address
Public Enquiries Karen Barnes karen.barnes@uct.ac.za +27214066008 K47.22 OMB, Groote Schuur Hospital, Observatory
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Acting Head of Division of Clinical Pharmacology
Role Name Email Phone Street address
Scientific Enquiries Jaishree Raman jaishreer@nicd.ac.za +27 11 3866374 1 Modderfontein Road, Sandringham
City Postal code Country Position/Affiliation
Johannesburg 2131 South Africa Senior Scientist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) Clinical Study Report,Statistical Analysis Plan,Study Protocol We shared the following with WWARN in 2019 Research proposals must be scientifically sound with adequate methodology to answer the question and should address a knowledge gap of value or potential value to malaria endemic communities, and/or to wider public health. The selected Data Subjects, populations and requested Data must be appropriate for the investigation
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://www.wwarn.org/working-together/sharing-accessing-data/accessing-data Yes 23/09/2021
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 23/09/2021
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information