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.: PACTR202308810518432 Date of Approval: 23/08/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Optimizing malarial treatment in HIV and kidney disease patients ( Optimahk trial)
Official scientific title Open-Label, Randomized Controlled Study Comparing The Efficacy And Tolerability Of Artemether-Lumefantrine And Artesunate-Amodiaquine In Hiv Patients With Kidney Disease Treated With Dolutegravir-Based Antiretroviral Therapy
Brief summary describing the background and objectives of the trial The burden of malaria/HIV coinfection is of great concern. The first-line drug management of malaria such as Artemether-Lumefantrine (AL) and Artesunate-Amodiaquine (AA) in HIV-infected patients is still faced with the challenges of resistance treatment failure, organ toxicity, and serious pharmacokinetic alterations when administered to HIV patients. Most HIV patients infected with malaria are likely to be treated with AL and AA given that they are first-line ACTs. Because HIV patients on ART are also very prone to chronic kidney disease. Consequently, the drug-disease interaction may contribute to reduced renal clearance of the antimalaria and eventually affect the efficacy and safety of AL and AA when administered. Despite this significance, studies documenting the effect of kidney dysfunction on the outcome of AL and AA in HIV patients are limited. Additionally, bearing in mind the rapid uptake of dolutegravir (DTG) -containing ART as the first-line treatment of HIV in Nigeria, there exists the potential drug-drug interaction (DDI) between ACT and DTG-based ART. Hence, this necessitates the evaluation of antimalarial drug utilization and comparative outcome studies of artemether-lumefantrine and artesunate-amodiaquine among HIV patients with kidney disease. This study aims to assess and compare the effects of kidney dysfunction on the effectiveness and adverse event profile of the 2 most commonly used artemisinin-based combination therapy (ACT) in HIV patients with malaria to optimize the therapy. The objectives include:1.To determine the efficacy and assess the safety of Artemether-Lumefantrine (AL) among malaria/HIV-coinfected patients with kidney disease. 2. To determine the efficacy and assess the safety of Artesunate-Amodiaquine (AA) among malaria/HIV-coinfected patients with kidney disease. 3. To compare the treatment outcome of Artemether-Lumefantrine (AL) and Artesunate-Amodiaquine (AA) among malaria/HIV-coinfected patients with kidney disease.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Optimahk
Disease(s) or condition(s) being studied Infections and Infestations,Kidney Disease
Sub-Disease(s) or condition(s) being studied HIV/AIDS,Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 15/08/2022
Actual trial start date 04/10/2022
Anticipated date of last follow up 06/09/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 120
Actual target sample size (number of participants)
Recruitment status 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
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Artemether lumefantrine group in HIV with kidney disease Artemether 20mg + lumefantrine 120mg, 3 days A 3-day treatment schedule with a total of 6 doses, four tablets as a single initial dose, 4 tablets again after 8 hours and then 4 tablets twice-daily (morning and evening) for the following 2 days (total course of 24 tablets) administered with food. All doses will be administered in the study site followed by 30 minutes’ observation – Direct observation therapy (DOT). 30 Active-Treatment of Control Group
Control Group Artemether lumefantrine group in HIV without kidney disease Artemether 20mg + lumefantrine 120mg 3 days A 3-day treatment schedule with a total of 6 doses, four tablets as a single initial dose, 4 tablets again after 8 hours, and then 4 tablets twice daily (morning and evening) for the following 2 days (total course of 24 tablets) administered with food. All doses will be administered at the study site followed by 30 minutes’ observation – Direct observation therapy (DOT). 30 Active-Treatment of Control Group
Experimental Group Artesunate amodiaquine group in HIV with kidney disease Artesunate 100 mg + Amodiaquine hydrochloride equivalent to Amodiaquine base 300 mg 3 days One tablet of artesunate and one tablet of amodiaquine in the morning and evening daily for 3 days for a total 12 tablets. All doses will be administered in the study site followed by 30 minutes’ observation – Direct observation therapy (DOT) 30
Experimental Group Artesunate amodiaquine group in HIV without kidney disease Artesunate 100 mg + Amodiaquine hydrochloride equivalent to Amodiaquine base 300 mg 3 days One tablet of artesunate and one tablet of amodiaquine in the morning and evening daily for 3 days for a total 12 tablets. All doses will be administered in the study site followed by 30 minutes’ observation – Direct observation therapy (DOT) 30
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Age 18 years and older. 2. HIV positive 3. Fever (axillary temperature ≥ 37.5°C), or history of fever in previous 48 hours; 4. Microscopic confirmation of asexual stages of P. falciparum or mixed infection or malaria parasite densities >2,000/Μl 5. Receiving ART for at least 3 months. 6. Having CKD as evident by GFR <60 mL/min/1.73m2 and/or proteinuria 7. Willingness to give informed consent. 1. Pregnancy. 2. Severe/complicated malaria. 3.Severe anaemia (<8.5 g/dl haemoglobin (Hb)); 4. Full course of AA or AL treatment or more than two doses of another antimalarial in the past four weeks. 5. Known hypersensitivity to artemisinin derivates, amodiaquine, artemether-lumefantrine, or raltegravir. 6. Patient on haemodialysis 7. Patient with a history of cardiac arrhythmias 8. Not willing to give informed consent 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 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 11/08/2022 Lagos University Teaching Hospital Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Idi-Araba Lagos 100254 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Efficacy outcome Parasite clearance time. Safety outcome Proportion of Adverse events (AEs) 0,1,2,3,7,14,21 and 28 day
Secondary Outcome Efficacy outcome 1. Fever clearance time. 2. Cure rate; 28-day Adequate clinical and parasitological response (ACPR) 3. Failure rate: •Early treatment failure (ETF), •Late clinical failure (LCF) •Late parasitological failure (LPF) Safety outcome 1. Serious adverse event (SAEs) - grades 3 and 4 2. Corrected QT (QTcF) interval prolongation 3. Change in hemoglobin concentration from baseline 4. Change in GFR from baseline 5. Change in liver transaminases from baseline. 0,1,2,3,7,14,21 and 28 day
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Lagos University Teaching Hospital Idi-araba Lagos Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
University of Lagos ACEDHARS Akoka Lagos Nigeria
Dr. Abdulwasiu Adeniyi Busari Idi-araba Lagos Nigeria
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Dr. Abdulwasiu A Busari Idiarab Lagos Nigeria Individual
Secondary Sponsor Prof Fatai .A. Fehintola UI Ibadan Nigeria Individual
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Abdulwasiu Busari busarial@yahoo.com +2348033011555 Aladesuru
City Postal code Country Position/Affiliation
Lagos Nigeria University of Lagos
Role Name Email Phone Street address
Public Enquiries Sodiq Adeniyi adeniyisodiq65@gmail.com +2348102032598 ikorodu
City Postal code Country Position/Affiliation
Lagos Nigeria University of Lagos
Role Name Email Phone Street address
Scientific Enquiries Fatai Fehintola fentolamine@gmail.com +2348064251270 UI
City Postal code Country Position/Affiliation
Ibadan Nigeria University of Ibadan
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the result reported, after deidentification (text, tables, figures, and appendices) Study Protocol Beginning 12 months and ending 36 months following article publication Investigators whose proposed use of the data has been approved by an independent review committee
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