Home » Trials » SLCTR/2017/021


A multi-center, double-blind, randomized, 24-month study, to compare the efficacy of doxycycline once daily for 6 weeks versus placebo in improving filarial lymphedema independent of active filarial infection -

SLCTR Registration Number

SLCTR/2017/021


Date of Registration

13 Jul 2017

The date of last modification

Jul 13, 2017



Application Summary


Scientific Title of Trial

A multi-center, double-blind, randomized, 24-month study, to compare the efficacy of doxycycline once daily for 6 weeks versus placebo in improving filarial lymphedema independent of active filarial infection


Public Title of Trial

A 24 Month Study to Compare Efficacy of Doxycycline vs Placebo for Improving Filarial Lymphedema in Sri Lanka


Disease of Health Condition(s) Studied

Chronic Lymphoedema due to Lymphatic Filariasis


Scientific Acronym

None


Public Acronym

None


Brief title

LeDoxy-SL


Universal Trail Number

None


Any other number(s) assigned to the trial and issuing authority

NCT02929134 (ClinicalTrials.gov); USAID Cooperative Agreement Number AID-OAA-A-14-00008; EC-17-002 (ERC: Colombo)


Trial Details


What is the research question being addressed?

Will the addition of Doxycycline hyclate to standard hygiene measures be more effective compared to a placebo in improving lymphoedema grade, circumference and skin thickness in males and females aged 14 to 65 years with lymphedema caused by filarial infections?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded


Control

Placebo


Assignment

Parallel


Purpose

Treatment


Intervention(s) planned

Study Settings (Sri Lanka):
Pohlena, Walgama and Madihe suburbs, Galle District Snowball sampling method will be used to complete recruitment.

Study design:
This (LEDOXY-SL) trial is designed as a randomized, controlled, observer-, provider- and patient-blinded multicenter superiority trial with two parallel groups and a primary endpoint of change in grade of lymphedema at 24 months. The population will be stratified according to the Grade (Early Grade 1-3; Late Grade 4-6). Randomization will be performed as block randomization within each center in blocks of (N=4-10) for each of the groups (early and late).

Intervention
Intervention arm will receive doxycycline hyclate tablets 200mg/daily for six weeks (100mg/day for ages 14-18 years and body weight 40-50kg)

Control arm will receive identical placebo tablets 100mg – 2 tablets/day for six weeks (1 tablet/day for ages 14-18 years and body weight 40-50kg)

Standard lymphedema management protocols based on the use of simple measures of hygiene (regular washing with soap and water, skin and nail care), use of topical antibiotics or antifungal agents, exercise and footwear will be continued in both arms.


Inclusion criteria

  1. Age > 14 years and <65 years, male or non-pregnant women of childbearing-potential using an approved, effective method of contraception before, during and for at least 2 weeks after the completion of the active intervention with doxycycline or placebo
  2. Able to give informed consent to participate in the trial
  3. Resident in endemic area for five years or more
  4. Body weight >40 kg
  5. Lymphedema of a limb Grade 1-6 measured on a 7-point scale (Dreyer G et al. 2002).
  6. Ability to use established standardized methods of hygiene and effectively applying it prior to the initiation of the drug treatment
  7. No evidence of severe or systemic co-morbidities except for features of filarial disease
  8. Normal laboratory profile
  9. Consent to storage of blood samples for study

Exclusion criteria

  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. (A pregnancy test will be conducted as part of the screening process to exclude pregnancy and repeated at 3 and 8 weeks. In addition, women of childbearing potential will be counseled against pregnancy during the treatment period)
  6. Clinical or laboratory evidence of hepatic or renal dysfunction or CNS disease
  7. Alcohol or drug abuse
  8. History of adverse reactions to doxycycline or other tetracyclines
  9. Patient has any situation or condition that may interfere with participation in the study as judged by the clinical investigator
  10. Chronic headache and current headache
  11. Persons who are currently taking doxycycline for other indications
  12. Lymphedema due to post-radiation, post-surgical and primary (congenital) lymphedema


Primary outcome(s)

Change in lymphedema grade at 24 months compared to baseline


Primary outcome(s) - Time of assessment(s)

At baseline and 24 months after commencement of the intervention


Secondary outcome

  1. Improvement or halt of progression (Lack of progression) of LE when examined 12 months after treatment onset
  2. Improvement of LE when examined 12 and 24 months after treatment onset
  3. Change of LE stages (reduction or increase) compared to baseline assessed at 12 and 24 months
  4. Change in the circumference of the affected limb from baseline
  5. Reduction in the frequency of acute dermato-lymphangio-adenitis (ADLA) attacks evaluated from 0-12 months and from 12-24 months after treatment onset
  6. Changes in skin thickness at 12 and 24 months compared to the baseline
  7. Change in angiogenic, pro-fibrotic or pro-inflammatory biomarkers at 12 and 24 months following doxycycline administration (at sites where these tests are done)

Secondary outcome(s) - Time of assessment(s)

  1. Improvement or halt of progression (Lack of progression) of LE when examined 12 months after treatment onset
  2. Improvement of LE when examined 12 and 24 months after treatment onset
  3. Change of LE stages (reduction or increase) compared to baseline assessed at 12 and 24 months
  4. Change in the circumference of the affected limb from baseline
  5. Reduction in the frequency of acute dermato-lymphangio-adenitis (ADLA) attacks evaluated from 0-12 months and from 12-24 months after treatment onset
  6. Changes in skin thickness at 12 and 24 months compared to the baseline
  7. Change in angiogenic, pro-fibrotic or pro-inflammatory biomarkers at 12 and 24 months following doxycycline administration (at sites where these tests are done)


Target number/sample size

200 patients with Grades 1-3 lymphedema (100 per arm) and 50 patients with grade 4-6 lymphedema (25 per arm)


Countries of recruitment

Sri Lanka


Anticipated start date

2017-07-23


Anticipated end date

2020-07-23


Recruitment status

Pending


State of ethics review approval

Approved by Ethics Review Committee, Faculty of Medicine, University of Colombo on 16.02.2017 (Ref: EC-17-002)


Funding source

United States Agency for International Development (USAID)



Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

T.C. Yahathugoda
Head / Senior Lecturer
Filariasis Research Unit, Department of Parasitology, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka
Tel: +94(0)912234801
Mob: +94(0)777900981
Fax: +94(0)912222314
tcyahath@yahoo.co.uk
http://www.medi.ruh.ac.lk/

Contact Person for Public Queries

T.C. Yahathugoda
Head / Senior Lecturer
Filariasis Research Unit, Department of Parasitology, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka
Tel: +94(0)912234801
Mob: +94(0)777900981
Fax: +94(0)912222314
tcyahath@yahoo.co.uk
http://www.medi.ruh.ac.lk/


Primary study sponsor/organization

Task Force for Global Health

325 Swanton Way Decatur, Georgia 30030-3001, USA
Tel: (800) 765-7173
Fax: (404) 371-1087
Mariana Stephens <mstephens@taskforce.org>
www.taskforce.org

Secondary study sponsor (If any)

None