Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial
| Autor: | Joseph Nelson Siewe Fodjo, Swabra Nakato, Germain Abhafule, Deogratias Wonya’Rossi, Robert Colebunders, Sonia Menon, An Hotterbeekx, Francoise Nyisi, Michel Mandro, Richard Lokonda, Jean Marie Jakwong, Deby Mukendi, Steven Haesendonckx, Alfred Dusabimana, Patrick Suykerbuyk, Jacques Meganck |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Nematoda RC955-962 Fevers Onchocerciasis Pathology and Laboratory Medicine Logistic regression law.invention Epilepsy 0302 clinical medicine Ivermectin Randomized controlled trial law Arctic medicine. Tropical medicine Medicine and Health Sciences Clinical endpoint Medicine Antiparasitic Agents Pharmaceutics Eukaryota 3. Good health Infectious Diseases Neurology Research Design Helminth Infections Democratic Republic of the Congo Anticonvulsants Drug Therapy Combination Female Onchocerca Public aspects of medicine RA1-1270 Research Article Neglected Tropical Diseases medicine.drug Adult medicine.medical_specialty Drug Research and Development Adolescent Clinical Research Design 030231 tropical medicine Research and Analysis Methods Young Adult 03 medical and health sciences Signs and Symptoms Drug Therapy Diagnostic Medicine Helminths Internal medicine Parasitic Diseases Humans Animals Clinical Trials Pharmacology business.industry Organisms Public Health Environmental and Occupational Health Biology and Life Sciences Tropical Diseases medicine.disease Invertebrates Randomized Controlled Trials Clinical trial Regimen 030104 developmental biology Onchocerca Volvulus Human medicine Adverse Events Clinical Medicine business |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS neglected tropical diseases PLOS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 14, Iss 1, p e0007966 (2020) |
| ISSN: | 1935-2735 1935-2727 |
| DOI: | 10.1371/journal.pntd.0007966 |
| Popis: | Introduction Recent findings from onchocerciasis-endemic foci uphold that increasing ivermectin coverage reduces the epilepsy incidence, and anecdotal evidence suggests seizure frequency reduction in persons with onchocerciasis-associated epilepsy, when treated with ivermectin. We conducted a randomized clinical trial to assess whether ivermectin treatment decreases seizure frequency. Methods A proof-of-concept randomized clinical trial was conducted in the Logo health zone in the Ituri province, Democratic Republic of Congo, to compare seizure frequencies in onchocerciasis-infected persons with epilepsy (PWE) randomized to one of two treatment arms: the anti-epileptic drug phenobarbital supplemented with ivermectin, versus phenobarbital alone. The primary endpoint was defined as the probability of being seizure-free at month 4. A secondary endpoint was defined as >50% reduction in seizure frequency at month 4, compared to baseline. Both endpoints were analyzed using multiple logistic regression. In longitudinal analysis, the probability of seizure freedom during the follow-up period was assessed for both treatment arms by fitting a logistic regression model using generalized estimating equations (GEE). Results Ninety PWE enrolled between October and November 2017 were eligible for analysis. A multiple logistic regression analysis showed a borderline association between ivermectin treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975–2.799; p = 0.062). There was no significant difference in the probability of experiencing >50% reduction of the seizure frequency at month 4 between the two treatment arms. Also, treatment with ivermectin did not significantly increase the odds of being seizure-free during the individual follow-up visits. Conclusion Whether ivermectin has an added value in reducing the frequency of seizures in PWE treated with AED remains to be determined. A larger study in persons with OAE on a stable AED regimen and in persons with recent epilepsy onset should be considered to further investigate the potential beneficial effect of ivermectin treatment in persons with OAE. Trial registration Registration: www.clinicaltrials.gov; NCT03052998. Author summary A proof-of-concept randomized clinical trial with a four month follow-up period, was conducted to investigate whether ivermectin had an added value in decreasing the frequency of seizures in onchocerciasis-infected persons with epilepsy who were also started on the anti-epileptic drug phenobarbital. The trial showed that ivermectin was not harmful but did not had an added beneficial effect over phenobarbital. A larger study in persons on a stable anti-epileptic treatment regimen with recent epilepsy onset should be considered to further investigate the potential beneficial effect of ivermectin treatment in persons with onchocerciasis-associated epilepsy. |
| Databáze: | OpenAIRE |
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