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.: PACTR201708002420261 Date of Approval: 11/07/2017
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Doxycycline to improve filarial lymphedema
Official scientific title Doxycycline 200mg/d vs. 100mg/d for 6 weeks to improve filarial lymphedema - a multinational, double-blind, randomized, placebo-controlled trial
Brief summary describing the background and objectives of the trial Lymphatic filariasis (LF), caused by infection with Wuchereria bancrofti, Brugia malayi and Brugia timori is a major neglected tropical disease (NTD) identified as one of WHO¿s 17 NTDs, has strong links with poverty and is associated with significant clinical morbidity and social stigma. The common clinical manifestations of the disease are hydrocele and lymphedema (LE). The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 following the adoption of the World Health Assembly Resolution (WHA 50.29) to eliminate the disease as a public health problem by 2020. The twin goals of the programme are: 1) to reduce microfilaremia (Mf) levels using mass drug administration (MDA) and thereby interrupt transmission and 2) to provide morbidity management to alleviate suffering for those who already have disease. The effect of DOX 200 in reversing or stopping the progression of LE of patients with stage 1-3, irrespective of their filarial infection¿s being active, provides an opportunity to include the drug as a new tool in LF morbidity management programs. Treatment with DOX 100 would also be less costly for health care providers if it would be administered to all patients affected by LE and it might lead to the involvement of more patients in morbidity programs. Therefore this trial in Ghana will add a third treatment arm to investigate whether reduction of the dosage of doxycycline to 100 mg/day for 6 weeks (DOX 100) has an effect similar or equivalent to 200 mg/day. The aims of the study is ¿to confirm the efficacy of a 6-week course of daily doxycycline 200mg on lack of progression of filarial LE ¿to reduce the dosage of doxycycline from 200mg/d to 100mg/d for 6 weeks for the treatment of filarial LE
Type of trial RCT
Acronym (If the trial has an acronym then please provide) LEDoxy
Disease(s) or condition(s) being studied lymphatic filariasis, lymphedema,Skin and Connective Tissue Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/10/2017
Actual trial start date 01/10/2017
Anticipated date of last follow up 31/12/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 420
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
ISRCTN14042737 ISRCTN Registry
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 The randomization lists will be generated by the manufacturer of the study drugs (Piramal, UK) using block randomization. Patients with LE stage 1-3 (Group A: N = 360) and LE stage 4-6 (Group B: N = 60) will be randomized separately. Consenting subjects will be allocated to treatment sequentially according to the randomization list with treatment allocation being provided in individual envelopes. At each trial site, trial participants, care providers, and outcome assessors as well as the data management located in Bonn, Germany will be blinded to the drugs received by the patients Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Treatment ¿DOX 200¿ Doxycycline 200mg/day 6 weeks Patients with lymphedema stage 1-3 caused by Wuchereria bancrofti who meet the inclusion/ exclusion criteria will be invited to participate in the treatment 120
Experimental Group Treatment ¿DOX 100¿ Doxycycline 100mg/d 6 weeks Patients with lymphedema stage 1-3 caused by Wuchereria bancrofti who meet the inclusion/ exclusion criteria will be invited to participate 120
Control Group Treatment ¿Placebo¿ (control) Placebo matching Doxycycline 6 weeks Patients with lymphedema stage 1-3 caused by Wuchereria bancrofti who meet the inclusion/ exclusion criteria will be invited to participate in the treatment 120 Placebo
Experimental Group Treatment Group B ¿DOX 200¿ Doxycycline 200mg/day 6 weeks Patients with lymphedema stage 4-6 caused by Wuchereria bancrofti who meet the inclusion/ exclusion criteria will be invited to participate 30
Control Group Treatment ¿Placebo¿ (control): B Placebo matching Doxycycline 6 weeks Patients with lymphedema stage 4-6 caused by Wuchereria bancrofti who meet the inclusion/ exclusion criteria will be invited to participate 30 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Lymphedema of at least one leg Grade 1-6 measured on a 7-point scale [3] 2. Age ¿ 14 years and ¿ 65 years 3. Men or non-pregnant women. If women of childbearing-potential, they must use an approved, effective method of contraception (including abstinence) before, during and for at least 2 weeks after the completion of the active intervention with doxycycline or placebo 4. Negative pregnancy test 5. Body weight ¿ 40 kg 6. Resident in LF endemic area for ¿ 2 years 7. Able and willing to give informed consent to participate in the trial 8. Ability to use established standardized methods of hygiene and effectively applying it prior to the initiation of the drug treatment 1. No lymphedema or lymphedema stage 7 2. Age < 14 years or > 65 years 3. Body weight < 40 kg 4. Pregnant or breastfeeding women 5. Women of childbearing potential not using an agreed method of contraception (including abstinence; oral contraceptives are not allowed because of interaction with trial drugs) 6. Clinical or biologic evidence of hepatic or renal dysfunction or disease of the central nervous system (CNS) 7. Evidence of severe comorbidities except for features of filarial disease 8. Alcohol or drug abuse 9. History of adverse reactions to doxycycline or other tetracyclines 10. Any significant condition (including medical and psychological/ psychiatric disorder) which in the opinion of the study investigator might interfere with the conduct of the study 11. History of photosensitivity reactions after taking drugs. 12. Concomitant medication with antacids containing aluminium, magnesium or sucralfate and not able to discontinue 13. Concomitant medication with other antibiotics than doxycycline and not able to discontinue 14. Concomitant medication with diuretics or sulfonylurea Concomitant medication with coumarin Laboratory values which will lead to exusion 1. Haemoglobin < 8 gm/dL 2. Neutrophil count <2 000/mm3 3. Platelet count <100 000/mm3 4. Creatinine > 2 times upper limit of normal 5. AST (GOT) > 2 times upper limit of normal 6. ALT (GPT) > 2 times upper limit of normal 7. y-GT > 2 times upper limit of normal 8. Positive urine pregnancy test 14 Year(s) 65 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
No Committee of Human Research, Publications and Ethics
Ethics Committee Address
Street address City Postal code Country
SMS, Room 7, Anotomy Block 3 Kumasi 000 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
No 12/07/2017 Committee of Human Research, Publications and Ethics
Ethics Committee Address
Street address City Postal code Country
SMS, Room 7, Anotomy Block 3 Kumasi 000 Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Lack of progression of LE (stage reduction or same stage as pre- treatment using the 7-point scale staging according to Dreyer e tal. examined 24 months after treatment onset 24 months after treatment onset
Secondary Outcome ¿ Lack of progression of LE (stage reduction or same stage as pre- treatment using the 7-point scale staging according to Dreyer et al examined 6 or 12 months after treatment onset 12 months after treatment onset
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kumasi Centre for Collaborative Research Asuogya South End, Kumasi 000 Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
Germany Federal Ministry of Education and Research Dag-Hammarskjo¿ld-Weg 1-5, 65760 Eschborn Berlin 65760 Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Kumasi Centre for Collaborative Research Asuogya South End, Kumasi 0000 Ghana University
COLLABORATORS
Name Street address City Postal code Country
Bonn University Hospital Sigmund Freud Str. 25 Bonn 53127 Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Alexander Yaw Debrah yadebrah@yahoo.com +233 20 9341317 Asuogya South End
City Postal code Country Position/Affiliation
kumasi 0000 Ghana Dean of faculty
Role Name Email Phone Street address
Public Enquiries Linda Batsa lindrousy@yahoo.com +233 208174244 Asuogya South End
City Postal code Country Position/Affiliation
Kumasi 0000 Ghana Coordinator
Role Name Email Phone Street address
Scientific Enquiries Alexander Yaw Debrah yadebrah@yahoo.com +233 20 9341317 Asuogya South End
City Postal code Country Position/Affiliation
kumasi Ghana Dean of faculty
REPORTING
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