Tags

Type your tag names separated by a space and hit enter

The safety of double- and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study.

Abstract

BACKGROUND

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings.

METHODS AND FINDINGS

Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 μg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites.

CONCLUSIONS

In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA.

TRIAL REGISTRATION

Clinicaltrials.gov registration number: NCT02899936.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Washington University, St. Louis, Missouri, United States of America.

    ,

    Washington University, St. Louis, Missouri, United States of America.

    ,

    Universitas Indonesia, Jakarta, Indonesia.

    ,

    Centers of Disease Control and Prevention, Atlanta, Georgia, United States of America.

    ,

    Universitas Indonesia, Jakarta, Indonesia.

    ,

    Washington University, St. Louis, Missouri, United States of America.

    ,

    Washington University, St. Louis, Missouri, United States of America.

    ,

    Murdoch Children's Research Institute, Melbourne, Australia.

    ,

    ICMR-Vector Control Research Centre, Puducherry, India.

    ,

    Case Western Reserve University, Cleveland, Ohio, United States of America.

    ,

    ICMR-Vector Control Research Centre, Puducherry, India.

    ,

    ICMR-Vector Control Research Centre, Puducherry, India.

    ,

    Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.

    ,

    Ministère de la Santé Publique et de la Population (MSPP), Port-au-Prince, Haïti.

    ,

    Washington University, St. Louis, Missouri, United States of America.

    ,

    Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea. Burnet Institute, Melbourne, Australia.

    ,

    Fiji Ministry of Health and Medical Services, Suva, Fiji.

    ,

    Washington University, St. Louis, Missouri, United States of America.

    ,

    Centers of Disease Control and Prevention, Atlanta, Georgia, United States of America.

    ,

    ICMR-Vector Control Research Centre, Puducherry, India.

    ,

    Murdoch Children's Research Institute, Melbourne, Australia.

    ,

    Universitas Indonesia, Jakarta, Indonesia.

    ,

    ICMR-Vector Control Research Centre, Puducherry, India.

    Source

    PLoS medicine 16:6 2019 Jun pg e1002839

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31233507

    Citation

    Weil, Gary J., et al. "The Safety of Double- and Triple-drug Community Mass Drug Administration for Lymphatic Filariasis: a Multicenter, Open-label, Cluster-randomized Study." PLoS Medicine, vol. 16, no. 6, 2019, pp. e1002839.
    Weil GJ, Bogus J, Christian M, et al. The safety of double- and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study. PLoS Med. 2019;16(6):e1002839.
    Weil, G. J., Bogus, J., Christian, M., Dubray, C., Djuardi, Y., Fischer, P. U., ... Subramanian, S. (2019). The safety of double- and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study. PLoS Medicine, 16(6), pp. e1002839. doi:10.1371/journal.pmed.1002839.
    Weil GJ, et al. The Safety of Double- and Triple-drug Community Mass Drug Administration for Lymphatic Filariasis: a Multicenter, Open-label, Cluster-randomized Study. PLoS Med. 2019;16(6):e1002839. PubMed PMID: 31233507.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The safety of double- and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study. AU - Weil,Gary J, AU - Bogus,Joshua, AU - Christian,Michael, AU - Dubray,Christine, AU - Djuardi,Yenny, AU - Fischer,Peter U, AU - Goss,Charles W, AU - Hardy,Myra, AU - Jambulingam,Purushothaman, AU - King,Christopher L, AU - Kuttiat,Vijesh Sridhar, AU - Krishnamoorthy,Kaliannagounder, AU - Laman,Moses, AU - Lemoine,Jean Frantz, AU - O'Brian,Katiuscia K, AU - Robinson,Leanne J, AU - Samuela,Josaia, AU - Schechtman,Kenneth B, AU - Sircar,Anita, AU - Srividya,Adinarayanan, AU - Steer,Andrew C, AU - Supali,Taniawati, AU - Subramanian,Swaminathan, AU - ,, Y1 - 2019/06/24/ PY - 2018/10/19/received PY - 2019/05/24/accepted PY - 2019/6/25/entrez PY - 2019/6/25/pubmed PY - 2019/6/25/medline SP - e1002839 EP - e1002839 JF - PLoS medicine JO - PLoS Med. VL - 16 IS - 6 N2 - BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings. METHODS AND FINDINGS: Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 μg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites. CONCLUSIONS: In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA. TRIAL REGISTRATION: Clinicaltrials.gov registration number: NCT02899936. SN - 1549-1676 UR - https://www.unboundmedicine.com/medline/citation/31233507/The_safety_of_double-_and_triple-drug_community_mass_drug_administration_for_lymphatic_filariasis:_A_multicenter,_open-label,_cluster-randomized_study L2 - http://dx.plos.org/10.1371/journal.pmed.1002839 DB - PRIME DP - Unbound Medicine ER -