A 24 Month Study, to Compare the Efficacy of Doxycycline vs. Placebo for Improving Filarial Lymphedema in Mali

NCT02927496 | Completed Phase 3 DMC

• 1 other identifier: LeDoxy2015_Mali
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Current lymphedema management protocols are 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. This is considered the "standard of care" in most endemic countries in the absence of any structured treatment programs. Previous controlled clinical trials and extensive field experience have shown the benefit of these measures in reducing the frequency of attacks of acute dermato-lymphangio-adenitis (ADLA) that drive the progression of lymphedema. In the present study, the progression of lymphedema in a group of patients who receive a six-week course of doxycycline will be compared with that of a group who receives doxycycline "look-alike" placebo tablets. However, both groups will be enrolled into a standardized "regimen of hygiene" described above. Thus, patients enrolled in the "placebo" group also will receive the current standard of care, and the placebo used in the study will help to identify the benefits of doxycycline on a background of simple hygiene measures. The regimens will be explained to all participants who will be trained to use established standardized methods of hygiene and be effectively applying it prior to the initiation of the drug treatment. In addition, patients will be evaluated at 3, 6, 12 and 24 months.. A common, generic SOP with handouts that describes methods and the training schedule will be used so that similar methods are employed across all sites.

Conditions

Lymphedema; Lymphatic Filariasis; Filariasis

Keywords

Lymphedema; Lymphatic Filariasis; Filariasis; Doxycycline

Outcome Measures

Primary Outcomes (1)

• Change in Lymphedema

  Change in lymphedema grade at 24 months compared to baseline

  24 month

Secondary Outcomes (1)

• Change in number of acute attacks

  24 months

Study Arms (2)

Doxycycline

ACTIVE COMPARATOR

The Doxycycline treated group will enroll 125 participants. 100 patients with Grades 1-3 lymphedema per study site (based on end point and duration) and up to 25 patients with grade 4-6 lymphedema/per study site. Each patient will receive Doxycycline hyclate 200 mg per day x 6 weeks for patients \>50 kg or 100 mg per day for patients \<50 kg).

Drug: Doxycycline

Placebo

PLACEBO COMPARATOR

The Placebo treated group will enroll 125 participants. 100 patients with Grades 1-3 lymphedema per study site (based on end point and duration) and up to 25 patients with grade 4-6 lymphedema/per study site. Each patient will receive matching tablets containing no active ingredients.

Drug: Placebo

Interventions

Doxycycline DRUG

Once daily tablet for 6 weeks: Active comparator: Doxycycline hyclate 200 mg per day x 6 weeks for patients \>50 kg or 100 mg per day for patients \<50 kg)

Also known as: Doxycycline hyclate

Doxycycline

Placebo DRUG

Once daily tablet for 6 weeks. Placebo comparator: matching tablets containing no active ingredients

Placebo

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients eligible for the trial must comply with all of the following at randomization:
• 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
• Able to give informed consent to participate in the trial (forms to be attached)
• Resident in endemic area for five years or more
• Body weight \>40 kg
• Lymphedema of a limb Grade 1-6 measured on a 7-point scale. (Appendix 1 for explanation of the grading system (Dreyer G et al. 2002).
• Ability to use established standardized methods of hygiene and effectively applying it prior to the initiation of the drug treatment
• No evidence of severe or systemic comorbidities except for features of filarial disease
• Normal laboratory profile (Appendix 3 investigations and the maximum or minimum limits in the case of hematological abnormalities - Site Specific)
• Consent to storage of blood samples for study

You may not qualify if:

• Patients are ineligible to participate in the trial, if they have any of the following:
• No lymphedema or lymphedema stage 7
• Age \< 14 years or \> 65 years
• Body weight \< 40 kg
• Pregnant or breastfeeding women
• 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)
• Clinical or laboratory evidence of hepatic or renal dysfunction or CNS disease
• Alcohol or drug abuse
• History of adverse reactions to doxycycline or other tetracyclines
• Patient has any situation or condition that may interfere with participation in the study as judged by the clinical investigator

Sponsors & Collaborators

• The Task Force for Global Health: lead
• United States Agency for International Development (USAID): collaborator

Study Sites (1)

International Centers for Excellence in Research-Mali, Filariasis Res. Unit.

Bamako, 1805, Mali

Location

Related Publications (4)

• Mand S, Debrah AY, Klarmann U, Batsa L, Marfo-Debrekyei Y, Kwarteng A, Specht S, Belda-Domene A, Fimmers R, Taylor M, Adjei O, Hoerauf A. Doxycycline improves filarial lymphedema independent of active filarial infection: a randomized controlled trial. Clin Infect Dis. 2012 Sep;55(5):621-30. doi: 10.1093/cid/cis486. Epub 2012 May 18.

  PMID: 22610930 RESULT

• Dreyer G, Dreyer P, Noroes J. [Recommendations for the treatment of bancroftian filariasis in symptomless and diseased patients]. Rev Soc Bras Med Trop. 2002 Jan-Feb;35(1):43-50. doi: 10.1590/s0037-86822002000100009. Portuguese.

  PMID: 11873261 RESULT

• Shenoy RK, Kumaraswami V, Suma TK, Rajan K, Radhakuttyamma G. A double-blind, placebo-controlled study of the efficacy of oral penicillin, diethylcarbamazine or local treatment of the affected limb in preventing acute adenolymphangitis in lymphoedema caused by brugian filariasis. Ann Trop Med Parasitol. 1999 Jun;93(4):367-77. doi: 10.1080/00034989958366.

  PMID: 10656038 RESULT

• Horton J, Klarmann-Schulz U, Stephens M, Budge PJ, Coulibaly Y, Debrah A, Debrah LB, Krishnasastry S, Mwingira U, Ngenya A, Wanji S, Weerasooriya M, Yahathugoda C, Kroidl I, Deathe D, Majewski A, Sullivan S, Mackenzie C, Nutman TB, Shott JP, Weil G, Ottesen E, Hoerauf A. The design and development of a multicentric protocol to investigate the impact of adjunctive doxycycline on the management of peripheral lymphoedema caused by lymphatic filariasis and podoconiosis. Parasit Vectors. 2020 Mar 30;13(1):155. doi: 10.1186/s13071-020-04024-2.

  PMID: 32228663 DERIVED

Related Links

• The Task Force for Global Health

MeSH Terms

Conditions

Lymphedema; Elephantiasis, Filarial; Filariasis

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Eric Ottesen, MD

  Neglected Tropical Disease Support Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neglected Tropical Diseases Center

Study Record Dates

• First Submitted: October 6, 2016
• First Posted: October 7, 2016
• Study Start: June 19, 2018
• Primary Completion: December 19, 2020
• Study Completion: December 19, 2020
• Last Updated: June 24, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)