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.: PACTR201906665550709 Date of Registration: 27/06/2019
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title IDA for Onchocerciasis
Official scientific title Safety and efficacy of combination therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) for individuals with onchocerciasis
Brief summary describing the background and objectives of the trial This study will provide preliminary data on the safety of IDA treatment in persons with onchocerciasis when it is administered after pre-treatment with IVM to clear or greatly reduce microfilariae from the skin and eyes. Widespread use of IDA following IVM pretreatment (I/IDA) has the potential to greatly accelerate elimination of LF in African countries that are coendemic for LF and onchocerciasis. This study will also assess the efficacy of IDA for killing and sterilizing adult filarial worms. An improved macrofilaricidal treatment would be a major advance for the global program to eliminate onchocerciasis. Since the safety and efficacy objectives are both very important, we have included dual primary objectives for the study.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Onchocerciasis
Purpose of the trial Combination therapies
Anticipated trial start date 01/08/2019
Actual trial start date
Anticipated date of last follow up 01/09/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 300
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
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Single dose of Ivermectin and Albendazole Two medications - Ivermectin (IVM) + Albendazole (ALB) - Single dose of oral IVM (150 µg/kg) plus oral ALB (400 mg) One time dose The comparator (control) arm will receive one oral dose of a combination of Ivermectin (IVM) and Albendazole (ALB) 100 Active-Treatment of Control Group
Experimental Group Single dose of oral Ivermectin and Diethylcarbamazine and Albendazole Combination dose of oral ivermectin (IVM) + diethylcarbamazine (DEC) + albendazole (ALB) "IDA" x 1 dose Single dose of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg) One dose of combination "IDA" One time oral dose of a combination of ivermectin (IVM) + diethylcarbamazine (DEC) + albendazole (ALB) 100
Experimental Group Three time oral doses of ivermectin diethylcarbamazine and albendazole A once daily dose of a combination of Ivermectin (IVM) + Diehtylcarbamzine (DEC) + Albedazole (ALB) for 3 consecutive days IDA x 3 doses (oral) Once daily for 3 days oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg) One dose per day for three consecutive days Oral dose of a combination of Ivermectin (IVM) + Diehtylcarbamzine (DEC) + Albedazole (ALB) once a day for 3 consecutive days 100
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Men and women 16 – 70 years (at the time of enrollment; ±2 years) of age previously enrolled in the Part 1 study and residing in the area of the study. 2. Participants must have at least 1 palpable subcutaneous nodule (onchocercoma). 3. Participants with baseline skin Mf counts ≥ 3Mf/mg at the time of enrollment into the Part 1 study (Part I, see above). 1. Pregnant and breastfeeding mothers within 1 month of giving birth 2. Severe eye disease at baseline including uveitis, severe glaucoma, , severe keratitis, and/or cataracts that interfere with visualization of the posterior segment of the eye as well as the list of ocular diseases as outlined below Individuals who are excluded with significant ocular disease will be referred to appropriate ophthalmological care in a health facility (the district hospital) or the any other health facility in Ghana, where affected subjects will obtain appropriate care (University hospital or private ophthalmologist). All ocular disease exclusion criteria apply to either eye. Bilateral disease is not necessary to exclude a participant. A participant will be excluded if any of the criteria are met for one eye. a.-j. Ocular exclusion criteria listed in full in the protocol (not possible to list here due to word limit). 3. Significant comorbidities such as renal insufficiency, liver failure, or any other acute or chronic illness identified by study clinicians and investigators that interferes with the participant’s ability to go to school or work or perform routine household chores. 4. Prior allergic / hypersensitivity reactions or intolerance to IVM, albendazole, or DEC. 5. Treatment with IVM outside of the study after the pre-treatment clearing dose provided in the Part I study. 6. >5 motile Mf in the anterior chamber in either eye at the time of enrollment (six months after pre-treatment with IVM). 7. Any Mf identified in the posterior segment of the eye at the time of enrollment (six months after pre-treatment with IVM). 8. Any other condition identified by study clinicians or investigators that may preclude participation in the study. Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 16 Year(s) 72 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 07/05/2019 Ghana Health Service Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
P.O. Box MB 190 Accra 0503303 Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety: To compare rates and types of severe adverse events (grade 3 or higher) that occur within 7 days following 1 day or 3 days of treatment with triple drug treatment (DEC with ivermectin and albendazole) with the comparator regimen of 1 day of treatment with ivermectin and albendazole in persons with active Onchocerca volvulus infections six months after pretreatment with ivermectin alone. Safety - baseline, Days 1-7 after Tx, Follow-up at 3 months after Tx
Primary Outcome Efficacy: To compare the effect of three treatment regimens for killing or sterilizing adult female O. volvulus worms based on the percentage of all adult female worms in nodules that are alive with embryos in the uterus 18 months after treatment. Efficacy - 18 months
Secondary Outcome Safety: 1. To compare rates of adverse events grade 3 or higher by treatment group that occur within 7 days of treatment in the subset of participants who have intraocular microfilariae just prior to treatment with IDA. 2. To compare rates of ocular adverse events (any grade) by treatment group that occur within 3 months of treatment with IDA Baseline, Days 1-7, 3 Months after Tx
Secondary Outcome Efficacy 1. To compare the effect of three treatment regimens for killing adult female O. volvulus worms based on the percentage of all adult female worms in nodules that are alive 18 months after treatment. 2. To compare the effects of three treatment regimens for complete clearance of microfilariae from skin snips 3, 12 and 18 months after treatment with IDA. 3. To compare the effects of three treatment regimens for preventing reappearance of microfilariae in the skin at 12, and 18 months after treatment with IDA. Efficacy at 3 months, 12 months, and 18 months after treatment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Onchocerciasis Chemotherapy Research Centre at Hohoe Municipal Hospital University of Health and Allied Sciences Hohoe Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 500 5th Ave N Seattle 98109 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Washington University in St. Louis 660 S Euclid Ave St Louis 63110 United States of America University
COLLABORATORS
Name Street address City Postal code Country
University of Health and Allied Sciences PMB 31 Ho Volta Ghana
Case Western Reserve University 10900 Euclid Ave 4983 Cleveland 44106 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Nicholas Opoku noopoku@uhas.edu.gh +233244776668 PMB 31
City Postal code Country Position/Affiliation
Hohoe 454855 Ghana Physician
Role Name Email Phone Street address
Public Enquiries Fidelis Anumu fanumu@uhas.edu.gh 233244061270 PMB 31
City Postal code Country Position/Affiliation
Ho Ghana Acting Head of Research Operations
Role Name Email Phone Street address
Scientific Enquiries Gary Weil g.j.weil@wustl.edu +13144547787 4444 Forest Park, Ste. 2212
City Postal code Country Position/Affiliation
St. Louis 63110 United States of America PI of DOLF Project and Infectious Disease Internist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data will be collected in a secure, ICH compliant, electronic data capture system. The participant key with unique identifiers will remain on site in a locked storage cabinet available only to the PI and the project manager. After being identified, these data will be shared among international collaborators and the sponsor according to the Data Sharing Agreement (outlined below in Key Access Criteria. As it isused in this description, de-identified data means that unique identifiers, specifically, names and house numbers, will be removed. Study participant information will include: unique study identification number, date of Informed Consent, date of birth, gender, village, other basic demographic information, height, weight, medical history, vital signs, physical exam findings, reported symptoms associated with adverse events related to study medications, nodule sample collected, microfilaria counts, and ocular and skin examinations (especially as they relate to onchocerciasis). Participant’s identity will be kept confidential. Participant’s names will not be collected in the EDC. Each study site will keep a separate enrollment log with the participant’s name and unique study identification number. The enrollment log will be stored in a secure and locked location, or in the case that this is an electronic log, it will be stored on password protected computers or devices and saved in an encrypted file. The endemic country PI or their designate will have access to the enrollment log to identify participants for follow-up. Other personal identifying information will be captured and stored using Excel database that will be secured with password protected laptops; only the UHAS PI and their designates will have access to personal identifying information. Personal identifiers will not be included in the datasets used for analysis. The participant’s unique barcode number will anonymously link data records. Informed Consent Form,Statistical Analysis Plan,Study Protocol Study protocol (with statistical analysis plan embedded in body of protocol) will be available in August 2019 Study Informed Consent Form will be available in August 2019 Investigators and their supporting governmental entities or research organization will own the data generated from this study. The Ghana principal investigator (PI) will be responsible for the study and data collection and therefore have authority over the data, unless otherwise stated by law or policies from the PI’s supporting institution. Only the local country PI will have ownership of the complete dataset with personal identifiers. The Ghana PI has the authority to share data with third-parties. Washington University in St. Louis will serve as the data coordinator for the DOLF Safety and efficacy of combination therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) for individuals with onchocerciasis study. De-identified electronic data will be uploaded from the Ghana study site and stored on servers managed by the electronic data capture company hired for this purpose, or on servers at Washington University. During the study access to the data will be password protected with user-specific access rights. Study investigators will be given individual user accounts to the database allowing them full view access to the data. Ghanaian Investigators will also have read/write access to the data. Only Ghanaian Investigators will have access to any participant keys or data sets with personal identifiers. Access to the de-identified dataset will be given to the identified DOLF partner scientists. At the end of the study the Ghana PI will be provided with their country’s dataset on password protected CDs or USB drives. The DOLF PI will archive the de-identified aggregate dataset for a minimum of 35 years. All primary data (including CRFs), whether electronic or on paper, should be stored in a secure location by the local country PI for a minimum of 3 years after the last participant has completed the study. This information will be retained for a longer period, however, if required by local regulations. It is understood that investigators and their supporting
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