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.: PACTR201908520097051 Date of Approval: 02/08/2019
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Efficacy and safety of Ivermectin for the treatment of Plasmodium falciparum infections in asymptomatic Gabonese adults
Official scientific title Efficacy and safety of Ivermectin for the treatment of Plasmodium falciparum infections in asymptomatic Gabonese adults
Brief summary describing the background and objectives of the trial Ivermectin has a potent anti-parasitic and anti-insecticide activity against many organisms including ecto- and endoparasites in animals and in humans. Malaria, a mosquito-borne disease caused by parasites of the genus Plasmodium, remains the most important parasitic disease in humans worldwide. It has been shown that ivermectin can reduce transmission of Plasmodium parasites by its activity against blood-sucking mosquitoes, but recent in vitro data suggests that ivermectin has also and effect on the erythrocytic stages of P. falciparum, but in vivo data are lacking. Besides its insecticidal activity, the excellent safety profile of ivermectin, which has been used for decades in mass drug administration programs, and a different mechanism of action compared to other antimalarials make ivermectin an interesting candidate for malaria control and elimination campaigns. This dose escalation study is designed to assess the activity of ivermectin on the parasitaemia of asymptomatic P. falciparum infections. The aim of this study is to investigate whether ivermectin is safe at a 3x300 µg/kg treatment course and can reduce or clear parasitaemia in participants infected with P. falciparum assessed by thick blood smear microscopy. Primary Objective(s): To assess the safety and tolerability of single- and multiple ascending doses of iver-mectin in volunteers with asymptomatic P. falciparum infection To assess the efficacy of ivermectin in participants with asymptomatic P. falciparum infection Secondary Objective(s): To compare efficacy of ivermectin 200μg/kg single dose versus two-day 200µg/kg treatment versus three-day 200μg/kg treatment versus three-day 300µg/kg treatment - To compare efficacy of ivermectin three-day 300µg/kg treatment compared to placebo - To compare safety and tolerability of ivermectin 200μg/kg single dose versus two-day 200µg/kg treatment versus three-day 200μg/kg treatment versus three-day 300µg/kg treatment - To compare safety and toler
Type of trial RCT
Acronym (If the trial has an acronym then please provide) IVERCURE
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 21/05/2019
Actual trial start date
Anticipated date of last follow up 31/03/2020
Actual Last follow-up date 07/10/2020
Anticipated target sample size (number of participants) 49
Actual target sample size (number of participants) 49
Recruitment status Completed
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 Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group safety group 200µg ivermectine once per day one day subjects will receive ivermectine for safety reason and will be include sequencially 5
Experimental Group safety group 200µg ivermectin once per day two day subjects will receive ivermectine for safety reason and will be include sequencially 5
Experimental Group safety group 200µg ivermectin once per day three days subjects will receive ivermectine for safety reason and will be include sequencially 5
Experimental Group Treatment group 300µg ivermectin once per day three days this group treatment will have randimized subjects and treatment is double blinde. The folluw-up still the same for all subject 17
Control Group Placebo control 300µg placebo once per day three days this group treatment will have appropriated randimization. treatment is double blinde and follow up will be the same 17 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Male or female, aged ≥ 18 years and body weight ≥ 45 kg - P. falciparum parasitaemia of 200 to 5000 parasites/µL - Asymptomatic malaria defined as: presence of P. falciparum mono-infection with absence of fever (axillary temperature <38.5 °C and absence of history of fever in the recent 24 hours and the week before inclusion) and other symptoms re-lated to malaria - Willingness to take part in the study and to sign the informed consent form - Active tuberculosis, or history of taking anti-tuberculosis medications within 12 months prior to screening - any Loa loa microfilaria infection detected by microscopy - AST/ALT > 2x the upper limit of normal range (ULN) - Taking an experimental drug in the last 4 weeks - Antimalarial treatment in the last 4 weeks - Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin) - Use of ivermectin within 30 days of study enrolment - Participants taking herbal medication within one week of screening - Known or suspected electrolyte imbalance, e.g. hypokalae-mia, hypocalcaemia or hypomagnesemia with clinical signif-icance - Moderate to severe anaemia (Haemoglobin level <8 g/dL) - Any known or suspected immunosuppressive or immunode-ficient condition, including human immunodeficiency virus (HIV) infection - Severe malnutrition (Body Mass Index (BMI) < 16.0) - Pregnant or nursing (lactating) women - Known chronic underlying disease such as sickle cell disease or severe cardiac impairment - Participants with serum creatinine ≥ 2 X ULN in the absence of dehydration. In case of dehydration, Participants with se-rum creatinine ≥ 2 X ULN after oral or parenteral rehydration - Participants with any psychiatric or neurological condition including substance abuse - Allergy to ivermectin Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Day(s) 70 Day(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 16/05/2019 Comite Ethique Institutionnel Centre de Recherches Medicales de Lambarene
Ethics Committee Address
Street address City Postal code Country
CERMEL Lambarene 1437 Gabon
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Time to 90% parasite reduction for at least 8 hours assessed by microscopy Number and occurrence of related SAE and Grade 3 AE from time of first administration of ivermectin until the end of the study 8 hours
Secondary Outcome Time to 90% parasite reduction assessed by qPCR Difference in AUC of parasitaemia until D7 Parasite clearance time, defined as time to parasitaemia <100 parasites/mL Number and occurrence of any AE from time of first admin-istration of ivermectin until the end of the study 8 hours
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre de Recherches Medicales de Lambarene CERMEL Lambarene Gabon
FUNDING SOURCES
Name of source Street address City Postal code Country
Centre de Recherches Medicales de Lambarene CERMEL Lambarene Gabon
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Centre de Recherches Medicales de Lambarene CERMEL Lambarene Gabon Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Jana Held 27 Wilhelmstrasse Tubingen Germany
Benjamin Mordmuller 27 Wilhelmstrasse Tubingen Germany
Ghyslain Mombo Ngoma cermel Lambarene Gabon
Lais Carvalho 27 Wilhelmstrasse Tubingen Germany
Dorothea Strabner 74 strasse Hamburg Germany
Wilfrid Ndoumba cermel Lambarene Gabon
Lia Betty Dimessa cermel Lambarene Gabon
Malick Akinosho cermel Lambarene Gabon
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Rella Zoleko Manego manegorella@yahoo.fr 0024707155748 CERMEL
City Postal code Country Position/Affiliation
Lambarene Gabon Centre de Recherche Medicale de Lambarene
Role Name Email Phone Street address
Scientific Enquiries Michael Ramharter ramharter@bnitm.de 00494042818511 74 strasse Bernhard Nocht
City Postal code Country Position/Affiliation
Hamburh Germany Bernhard Nocht Institute for Tropical Medicine
Role Name Email Phone Street address
Public Enquiries Michael Ramharter ramharter@bnitm.de 00494042818511 74 strasse Bernhard Nocht
City Postal code Country Position/Affiliation
Hamburh Germany Bernhard Nocht Institute for Tropical Medicine
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes IPD that underlie the results reported in this study after deidentification (text, tables, figures, and appendices). With Whom? Researchers who provide a methodologically sound proposal. For what type of research? To achieve aims in the approved proposal and for individual participant meta-analysis Informed Consent Form,Study Protocol Beginning 3 months and ending 5 years following article publication IPD meta-analysis and analysis to achieve the aims in the approved proposal
URL Results Available Results Summary Result Posting Date First Journal Publication Date
www.cermel.org 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