Death to Onchocerciasis and Lymphatic Filariasis (DOLF) Triple Drug Therapy for Lymphatic Filariasis

NCT02899936 | Completed DMC

• 1 other identifier: 201607068
• Study Type: interventional
• Target: 23,789
• Locations: 4 countries
• Sites: 4

Brief Summary

The DOLF Triple Drug Therapy for Lymphatic Filariasis study will determine the frequency, type and severity of adverse events following triple-drug therapy (IVM+DEC+ALB, IDA) compared to the standard two-drug treatment (DEC+ALB, DA) in infected and uninfected individuals in a community in 5 different countries. The objective is to acquire safety, efficacy, and acceptability data to assess the safety and acceptability of the IDA drug combination.

Conditions

Lymphatic Filariasis

Keywords

Mass drug administration; Safety Data

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by modified CTCAE v4.0 scale

  To determine the frequency, type and severity of adverse events following triple-drug therapy Ivermectin, Diethylcarbamazine and Albendazole (IVM+DEC+ALB, IDA) compared to the standard two-drug treatment Diethylcarbamazine and Albendazole (DEC+ALB, DA) in infected and uninfected individuals in a community as assessed by modified CTCAE v4.0 scale.

  within 7 days of drug administration

Secondary Outcomes (4)

• Number of participants with clearance of microfilaremia (MF) as measured with microfilaremia night blood smear testing (finger prick - 60ul)

  baseline (pre-treatment), within 7 days of drug administration and follow up at 12 months

• Number of participants Filarial Test Strip (FTS) and/or MF positive as tested with FTS and night blood smears with treatment-related adverse events as assessed by modified CTCAE v4.0 scale

  baseline (pre-treatment), within 7 days of drug administration and follow up at 12 months

• Community acceptance will be measured using on a survey using likert scale questions based on perception of efficacy, intent to participate and relevance of the treatment.

  6-8 months

• Prevalence of STH (hookworm, ascaris, trichuris and strongyloides) as measured by Kato-katz or PCR at baseline and 12 months after treatment

  Stool collected at baseline (pre-treatment), 4 weeks (individual response), and 12 months (community prevalence).

Study Arms (2)

2 drug dose - DA

ACTIVE COMPARATOR

Drug treatment with two-drug regimen diethylcarbamazine and albendazole (DA)

Drug: 2 drug dose - DA

3 drug dose - IDA

EXPERIMENTAL

Triple-drug regimen Ivermectin, diethylcarbamazine and albendazole (IDA)

Drug: 3 drug dose - IDA

Interventions

3 drug dose - IDA DRUG

Lymphatic Filariasis Mass Drug Administration (MDA) with triple drug therapy of ivermectin, diethylcarbamazine, and albendazole (IDA)

Also known as: IDA

3 drug dose - IDA

2 drug dose - DA DRUG

Lymphatic Filariasis Mass Drug Administration (MDA) with the currently used standard of care combination drug therapy of diethylcarbamazine, and albendazole (DA)

Also known as: DA

2 drug dose - DA

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 5 years, male or female for IDA arm and age \> 2 years for DA arm.
• Able to provide informed consent to participate in the trial (forms to be attached)
• No evidence of severe or systemic co-morbidities except for features of filarial disease

You may not qualify if:

• Age \< 5 years (ivermectin is contraindicated in children below 5 years of age) for IDA arm and age \< 2 years for DA arm
• Pregnant women (DEC, ivermectin and albendazole are contraindicated in pregnancy)
• Severe chronic illness (for example, chronic renal failure, inability to care for oneself with activities of daily living)
• History of previous allergy to MDA drugs
• For rest of countries:
• Age ≥ 5 years, for IDA and DA arms (males and females).
• Able to provide informed consent or give parental consent for minors to participate in the trial
• No evidence of severe or systemic co-morbidities except for features of filarial disease
• Age \< 5 years (ivermectin is not approved for use in children less than 5 years of age)
• Unable to provide informed consent or give parental consent for minors to participate in the trial
• Pregnant women (DEC, ivermectin and albendazole are not known to be safe for use during pregnancy)
• Severe chronic illness (chronic renal insufficiency, severe chronic liver disease, or any illness that is severe enough to interfere with activities of daily living)
• History of previous allergy to MDA drugs

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Case Western Reserve University: collaborator
• Indian Council of Medical Research: collaborator

Study Sites (4)

Ministere de la Sante Publique et de la Population

Port-au-Prince, Haiti

Location

Vector Control Research Centre

Puducherry, 605006, India

Location

Universitas Indonesia

Jakarta, Indonesia

Location

Papua New Guinea Institute for Medical Research

Madang, Papua New Guinea

Location

Related Publications (17)

• World Health Organization (1997). Elimination of lymphatic filariasis as a public health problem - resolution of the executive board of the WHO.

  BACKGROUND

• Thomsen EK, Sanuku N, Baea M, Satofan S, Maki E, Lombore B, Schmidt MS, Siba PM, Weil GJ, Kazura JW, Fleckenstein LL, King CL. Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis. Clin Infect Dis. 2016 Feb 1;62(3):334-341. doi: 10.1093/cid/civ882. Epub 2015 Oct 20.

  PMID: 26486704 BACKGROUND

• Gyapong JO, Kumaraswami V, Biswas G, Ottesen EA. Treatment strategies underpinning the global programme to eliminate lymphatic filariasis. Expert Opin Pharmacother. 2005 Feb;6(2):179-200. doi: 10.1517/14656566.6.2.179.

  PMID: 15757416 BACKGROUND

• 489 Global programme to eliminate lymphatic filariasis: progress report, 2014. Wkly Epidemiol Rec. 2015 Sep 18;90(38):489-504. No abstract available. English, French.

  PMID: 26387149 BACKGROUND

• Oscar R, Lemoine JF, Direny AN, Desir L, Beau de Rochars VE, Poirier MJ, Varghese A, Obidegwu I, Lammie PJ, Streit TG, Milord MD. Haiti National Program for the elimination of lymphatic filariasis--a model of success in the face of adversity. PLoS Negl Trop Dis. 2014 Jul 17;8(7):e2915. doi: 10.1371/journal.pntd.0002915. eCollection 2014 Jul. No abstract available.

  PMID: 25032697 BACKGROUND

• de Rochars MB, Kanjilal S, Direny AN, Radday J, Lafontant JG, Mathieu E, Rheingans RD, Haddix AC, Streit TG, Beach MJ, Addiss DG, Lammie PJ. The Leogane, Haiti demonstration project: decreased microfilaremia and program costs after three years of mass drug administration. Am J Trop Med Hyg. 2005 Nov;73(5):888-94.

  PMID: 16282299 BACKGROUND

• Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000;121 Suppl:S113-32. doi: 10.1017/s0031182000007290.

  PMID: 11386684 BACKGROUND

• Goa KL, McTavish D, Clissold SP. Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs. 1991 Oct;42(4):640-58. doi: 10.2165/00003495-199142040-00007.

  PMID: 1723366 BACKGROUND

• Edwards G. Ivermectin: does P-glycoprotein play a role in neurotoxicity? Filaria J. 2003 Oct 24;2 Suppl 1(Suppl 1):S8. doi: 10.1186/1475-2883-2-S1-S8.

  PMID: 14975065 BACKGROUND

• Ottesen EA, Campbell WC. Ivermectin in human medicine. J Antimicrob Chemother. 1994 Aug;34(2):195-203. doi: 10.1093/jac/34.2.195.

  PMID: 7814280 BACKGROUND

• Awadzi K, Edwards G, Duke BO, Opoku NO, Attah SK, Addy ET, Ardrey AE, Quartey BT. The co-administration of ivermectin and albendazole--safety, pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2003 Mar;97(2):165-78. doi: 10.1179/000349803235001697.

  PMID: 12803872 BACKGROUND

• Ottesen EA. Efficacy of diethylcarbamazine in eradicating infection with lymphatic-dwelling filariae in humans. Rev Infect Dis. 1985 May-Jun;7(3):341-56. doi: 10.1093/clinids/7.3.341.

  PMID: 3895352 BACKGROUND

• Noroes J, Dreyer G, Santos A, Mendes VG, Medeiros Z, Addiss D. Assessment of the efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo. Trans R Soc Trop Med Hyg. 1997 Jan-Feb;91(1):78-81. doi: 10.1016/s0035-9203(97)90405-3.

  PMID: 9093637 BACKGROUND

• Laman M, Tavul L, Karl S, Kotty B, Kerry Z, Kumai S, Samuel A, Lorry L, Timinao L, Howard SC, Makita L, John L, Bieb S, Wangi J, Albert JM, Payne M, Weil GJ, Tisch DJ, Bjerum CM, Robinson LJ, King CL. Mass drug administration of ivermectin, diethylcarbamazine, plus albendazole compared with diethylcarbamazine plus albendazole for reduction of lymphatic filariasis endemicity in Papua New Guinea: a cluster-randomised trial. Lancet Infect Dis. 2022 Aug;22(8):1200-1209. doi: 10.1016/S1473-3099(22)00026-3. Epub 2022 May 6.

  PMID: 35533701 DERIVED

• Tavul L, Laman M, Howard C, Kotty B, Samuel A, Bjerum C, O'Brian K, Kumai S, Amuga M, Lorry L, Kerry Z, Kualawi M, Karl S, Makita L, John LN, Bieb S, Wangi J, Weil GJ, Goss CW, Tisch DJ, Pomat W, King CL, Robinson LJ. Safety and efficacy of mass drug administration with a single-dose triple-drug regimen of albendazole + diethylcarbamazine + ivermectin for lymphatic filariasis in Papua New Guinea: An open-label, cluster-randomised trial. PLoS Negl Trop Dis. 2022 Feb 9;16(2):e0010096. doi: 10.1371/journal.pntd.0010096. eCollection 2022 Feb.

  PMID: 35139070 DERIVED

• Supali T, Djuardi Y, Christian M, Iskandar E, Alfian R, Maylasari R, Destani Y, Lomiga A, Minggu D, Lew D, Bogus J, Weil GJ, Fischer PU. An open label, randomized clinical trial to compare the tolerability and efficacy of ivermectin plus diethylcarbamazine and albendazole vs. diethylcarbamazine plus albendazole for treatment of brugian filariasis in Indonesia. PLoS Negl Trop Dis. 2021 Mar 29;15(3):e0009294. doi: 10.1371/journal.pntd.0009294. eCollection 2021 Mar.

  PMID: 33780481 DERIVED

• Weil GJ, Bogus J, Christian M, Dubray C, Djuardi Y, Fischer PU, Goss CW, Hardy M, Jambulingam P, King CL, Kuttiat VS, Krishnamoorthy K, Laman M, Lemoine JF, O'Brian KK, Robinson LJ, Samuela J, Schechtman KB, Sircar A, Srividya A, Steer AC, Supali T, Subramanian S; DOLF IDA Safety Study Group. The safety of double- and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study. PLoS Med. 2019 Jun 24;16(6):e1002839. doi: 10.1371/journal.pmed.1002839. eCollection 2019 Jun.

  PMID: 31233507 DERIVED

Related Links

• National Vector Borne Disease Control Programme (2015)

MeSH Terms

Conditions

Elephantiasis, Filarial

Condition Hierarchy (Ancestors)

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

Study Officials

• Gary Weil, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Christopher King, MD PHD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2016
• First Posted: September 14, 2016
• Study Start: July 1, 2016
• Primary Completion: April 27, 2017
• Study Completion: May 31, 2018
• Last Updated: December 31, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: Manuscripts should be submitted for publication no later than one year following the date of the "last patient/last visit". Some DOLF studies include follow-up studies that continue after the primary end point of the study. There is no need to wait for these studies to be completed in order to publish the primary data. (In the case of the IDA studies, safety data should be prepared for publication prior to the acceptability and efficacy studies.)
• Access Criteria: Investigators and their supporting institution that conduct research with financial support from Bill \& Melinda Gates Foundation (BMGF) will share de-identified data with partner scientists. Results from multiple study sites will be combined so that they can be considered in aggregate. Aggregated data and summary results may be shared with the World Health Org, BMGF, pharmaceutical donors, and others involved in the Global Prog to Eliminate Lymphatic Filariasis even prior to the publication of results. We will follow US National Institutes of Health (NIH) guidelines regarding data sharing with scientists outside of the project. Datasets used for published results will be shared publically through a journal or other open source data repository. De-identified data will be shared outside of DOLF. Data sharing requests from third-parties must have the approval of the local country PI. The study's primary results should be published before data will be shared with third-parties.

Locations

ID (1); IN (1); HA (1); PA (1)