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.: PACTR202009704006025 Date of Approval: 09/09/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title The efficacy of Rifampicin plus Albendazole against Lymphatic filariasis and Onchocerciaisis.
Official scientific title The efficacy of Rifampicin 35mg/Kg/d plus Albendazole 400mg/d given for 7 or 14 days against Lymphatic Filariasis and Onchocerciasis– a randomized, controlled, parallel-group, open-label, phase II pilot trial
Brief summary describing the background and objectives of the trial Background: The achievements of onchocerciasis and lymphatic filariasis (LF) mass drug administration (MDA) programmes have considerably reduced transmission and led to the formulation of the goal to eliminate these diseases. The development and implementation of new drugs or improved regimens will increase cost effectiveness by avoiding unnecessary treatments of uninfected individuals within the MDA schemes. This is needed in “end-game” scenarios when switching from MDA to a “Test and Treat” scheme. A major problem with the current MDA is that the drugs have limited efficacy against adult worms and do not permanently stop microfilarial production. The bacterial endosymbiont Wolbachia in most filarial worms is essential for the survival of the worms. In a pre-clinical trial, a combination of antiwolbachial drug, Rifampicin and Albendazole produced substantial synergy, and this synergy leads to long-term sterilizing effects and reduced treatment course to 7 days, and mediated an accelerated macrofilaricidal effect. As there is a lack of critical mass of scientists in neglected tropical diseases (NTDs) we also propose to expand capacity through this research programme. AIMS: The main objective is to show efficacy of the combination of Rifampicin plus Albendazole using PCR and immunohistology compared to treatment with Albendazole or ivermectin alone. PRIMARY ENDPOINT: Proportions of living female worms with normal vs. interrupted embryogenesis assessed by histology or PCR after 18-20 months. SECONDARY ENDPOINTS: Proportion of study participants with absence of microfilariae in the skin or blood, assessed 4-6 and 18-20 months compared to pre-treatment.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ASTAWOL
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Lymphatic filariasis and onchocerciasis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/10/2020
Actual trial start date 01/10/2020
Anticipated date of last follow up 31/01/2024
Actual Last follow-up date 31/12/2024
Anticipated target sample size (number of participants) 240
Actual target sample size (number of participants) 189
Recruitment status Active, not recruiting
Publication URL 0
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 Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Rifampicin 35mg/kg/d 7 days It is be daily observed treatment (DOT) 60
Experimental Group Rifampicin 35mg/kg/d 14 days Daily Observed treatment (DOT) 60
Experimental Group Zentel 400mg/day 14 days Daily Observed treatment 60
Control Group ivermectin 150ug/Kg once a year This is the standard treatment in the community 60 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Lymphatic filariasis Participants will only be included in the study if they meet all of the following criteria: • Willingness to participate in the study by signing the Informed Consent Form (ICF) • 18-55 years • Body weight > 45kg • Positive for CFA detected by Fliarial Test Strip (FTS) and with or without filarial dance sign (FDS) detected by Ultrasonography (USG) measurement • MF-positive • Good general health without any clinical condition requiring medication • No previous history of tuberculosis • Participants with the ability to follow study instructions and who are likely to attend and complete all required visits Onchocerciasis Participants will only be included in the study if they meet all of the following criteria: • Willingness to participate in the study by signing the Informed Consent Form (ICF) • 18-55 years • Body weight > 45kg • Presence of at least 1 medium-sized onchocercoma detected by palpation • MF-positive • Good general health without any clinical condition requiring medication • No previous history of tuberculosis • Participants with the ability to follow study instructions and are likely to attend and complete all required visits General Exclusion Criteria: • Participants not able to give consent • Participants who are unable to understand the nature, scope, significance and consequences of this clinical trial • Participants taking concomitant medication that interferes with study drugs (at the discretion of trial clinician) • Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical structure (rifampicin or any member of the rifamycins) • Simultaneous participation in any clinical trial involving administration of an investigational medicinal product within 30 days prior to clinical trial beginning • Participants with a physical or psychiatric condition which at the investigator’s discretion may put the subject at risk, may confound the trial results, or may interfere with the subject’s participation in this clinical trial • Known or persistent abuse of medication, drugs or alcohol Laboratory Exclusion Criteria: • Evidence of clinically significant neurological, cardiac, pulmonary, hepatic or renal disease as far as can be assessed by history of participants, physical examination, and/or laboratory examinations • Evidence of acute Hepatitis A and acute or chronic Hepatitis B or C • Laboratory evidence of liver disease (AST, ALT and γGT greater than 1.5 times the upper limit of normal • Laboratory evidence of renal disease (eGRF <60ml/min/1.732M2) • Laboratory evidence of leukopenia (leukocytes < lower limit of normal) Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 55 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 05/01/2021 Committee on Human Research Publication and Ethics
Ethics Committee Address
Street address City Postal code Country
Research and Development Division, Ghana Health Service, P. O. Box MB190, Accra Accra 0000 Ghana
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 05/01/2021 GHANA HEALTH SERVICE ETHICS REVIEW COMMITTEE
Ethics Committee Address
Street address City Postal code Country
Research and Development Division, UPO, Accra Accra 0000 Ghana
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 01/02/2021 Ghana Food and Drugs Authority
Ethics Committee Address
Street address City Postal code Country
GA-237-73,16 Accra 0000 Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Primary Outcomes (Lymphatic filariasis trial): To determine the: - Dead adult worms and MF assessed by the levels of CFA and MF 20 months after treatment onset (where day 0 is start of drug administration). - Absence of Wolbachia endobacteria in MF assessed by PCR 4 months after treatment onset Primary Outcomes (Onchocerciasis trial): To determine the: - Proportion of dead adult worms and MF assessed by immunohistology 20 months after treatment onset (where day 0 is start of drug administration). - Absence of Wolbachia endobacteria in adult female worms assessed by immunohistology 20 months after treatment onset 12 months and 18 months for lymphatic filariasis and 12 months and 20 months for onchocerciasis
Secondary Outcome Secondary Outcomes (Lymphatic filariasis trial): To determine the: - Reduction of Wolbachia bacteria in MF worms assessed by PCR 4, 12 and 18 months after treatment onset. - Absence of Wolbachia bacteria in MF worms assessed by PCR 4, 12 and 18 months after treatment onset. - Reduction of CFA in adult worms assessed by Alere filarial antigen test strips and TropBio ELISA 12 and 18 months after treatment onset. - Reduction of microfilariae in the blood 4, 12 and 18 months after treatment onset. - Absence of microfilariae in the blood at 4, 12 and 18 months after treatment onset. - Absence or reduction of filarial dance sign (FDS) detected by scrotal ultrasound 4, 12 and 18 months after treatment onset. - Adverse events (AEs) as well as serious adverse events (SAEs) in response to the different treatments will be assessed and described in the scope of the daily observed treatment (DOT). Secondary Outcomes (Onchocerciasis trial): • Assessment of embryogenesis in female worms by histology 20 months after treatment onset • Determination of number of nodules (onchocercomata) with free living microfilariae assessed by histology 20 months after treatment onset • Evaluation of worm embryogenesis assessed by histology 20 months after treatment onset a) Normal embryos b) Degenerated embryos c) no embryos (oocytes only or uterus empty • Assessment of number of live/ dead worms (macrofilaricidal activity) through histology 20 months after treatment onset • Insemination of female worms assessed by histology 20 months after treatment onset • Absence of Wolbachia bacteria (as a non-quantitative parameter) in adult worms assessed by immunohistology (using antisera against Wolbachia surface protein) as described for our previous trials [9] 20 months after treatment • Reduction of Wolbachia bacteria in adult worms assessed by immunohistology 20 months after treatment onset • Reduction of Wolbachia bacteria in adult worms assessed by PCR 20 months after treatment 4, 12 and 18-20 months after treatment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kumasi Centre for Collaborative Research in Tropical Medicine KCCR, South Asuogya Road, KNUST Kumasi 0000 Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP 2509 AA, The Hague 2509 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Kumasi Centre for Collaborative Research KCCR, Asuogya South End Road, KNUST Kumasi 0000 Ghana University
COLLABORATORS
Name Street address City Postal code Country
Prof Achim Hoerauf Venusberg-Campus 1, University of Bonn Hospital Bonn Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Alexander Yaw Debrah yadebrah@yahoo.com 00233209341317 KCCR, Asuogya South End Road, KNUST
City Postal code Country Position/Affiliation
Kumasi 0000 Ghana Dean of Faculty
Role Name Email Phone Street address
Public Enquiries Jubin Osei Mensah jubinom@yahoo.com 00233209099572 KCCR, Asuogya South End Road, KNUST
City Postal code Country Position/Affiliation
Kumasi 0000 Ghana Project Manager
Role Name Email Phone Street address
Scientific Enquiries Linda Batsa Debrah lindrousy@yahoo.com 00233208174244 KCCR, Asuogya South End Road, KNUST
City Postal code Country Position/Affiliation
Kumasi 0000 Ghana Project Coordinator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The Individual patient data of de-identified individual trial participant data will be shared. This will be done at least after 24 months after the trial is over. It will be shared with the public. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Immediately following publication, no end date Anyone who wishes to access the data will be given access for any purpose. Proposal may be submitted following article publication. After 12 months of publication the data will be available in our University’s data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing date may be found at our university repository.
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 - 10/04/2025 Result - 10/04/2025 Result - 11/04/2025 Result - 11/04/2025
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information