Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial.
<h4>Background</h4>Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-06-01
|
| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0010123 |
| _version_ | 1811155433764683776 |
|---|---|
| author | Gathsaurie Neelika Malavige Chandima Jeewandara Ananda Wijewickrama Dumni Gunasinghe Sameera D Mahapatuna Chathurika Gangani Vimalahan Vimalachandran Geethal Jayarathna Yashoda Perera Chandanie Wanigatunga Harsha Dissanayake Shamini Prathapan Eranga Narangoda Damayanthi Idampitiya Laksiri Gomes Samurdhi Wickramanayake Pramodth Sahabandu Graham S Ogg |
| author_facet | Gathsaurie Neelika Malavige Chandima Jeewandara Ananda Wijewickrama Dumni Gunasinghe Sameera D Mahapatuna Chathurika Gangani Vimalahan Vimalachandran Geethal Jayarathna Yashoda Perera Chandanie Wanigatunga Harsha Dissanayake Shamini Prathapan Eranga Narangoda Damayanthi Idampitiya Laksiri Gomes Samurdhi Wickramanayake Pramodth Sahabandu Graham S Ogg |
| author_sort | Gathsaurie Neelika Malavige |
| collection | DOAJ |
| description | <h4>Background</h4>Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever (DHF) in patients with acute dengue.<h4>Methods and findings</h4>A phase 2, randomised, double blind, placebo controlled clinical trial was carried out in patients with acute dengue in Sri Lanka in an outpatient setting. Patients with ≤3 days since the onset of illness were either recruited to the treatment arm of oral rupatadine 40mg for 5 days (n = 123) or the placebo arm (n = 126). Clinical and laboratory features were measured daily to assess development of DHF and other complications. 12 (9.7%) patients developed DHF in the treatment arm compared to 22 (17.5%) who were on the placebo although this was not significant (p = 0.09, relative risk 0.68, 95% CI 0.41 to 1.08). Rupatadine also significantly reduced (p = 0.01) the proportion of patients with platelet counts <50,000 cells/mm3 and significantly reduced (p = 0.04) persisting vomiting, headache and hepatic tenderness (p<0.0001) in patients. There was a significant difference in the duration of illness (p = 0.0002) although the proportion of individuals who required hospital admission in both treatment arms. Only 2 patients on rupatadine and 3 patients on the placebo developed shock, while bleeding manifestations were seen in 6 patients on rupatadine and 7 patients on the placebo.<h4>Conclusions</h4>Rupatadine appeared to be safe and well tolerated and showed a trend towards a reducing proportion of patients with acute dengue who developed DHF. Its usefulness when used in combination with other treatment modalities should be explored.<h4>Trial registration</h4>International Clinical Trials Registration Platform: SLCTR/2017/024. |
| first_indexed | 2024-04-10T04:32:57Z |
| format | Article |
| id | doaj.art-78b5d37a600841c2af7552717752a95c |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-04-10T04:32:57Z |
| publishDate | 2022-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-78b5d37a600841c2af7552717752a95c2023-03-10T05:32:38ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352022-06-01166e001012310.1371/journal.pntd.0010123Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial.Gathsaurie Neelika MalavigeChandima JeewandaraAnanda WijewickramaDumni GunasingheSameera D MahapatunaChathurika GanganiVimalahan VimalachandranGeethal JayarathnaYashoda PereraChandanie WanigatungaHarsha DissanayakeShamini PrathapanEranga NarangodaDamayanthi IdampitiyaLaksiri GomesSamurdhi WickramanayakePramodth SahabanduGraham S Ogg<h4>Background</h4>Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever (DHF) in patients with acute dengue.<h4>Methods and findings</h4>A phase 2, randomised, double blind, placebo controlled clinical trial was carried out in patients with acute dengue in Sri Lanka in an outpatient setting. Patients with ≤3 days since the onset of illness were either recruited to the treatment arm of oral rupatadine 40mg for 5 days (n = 123) or the placebo arm (n = 126). Clinical and laboratory features were measured daily to assess development of DHF and other complications. 12 (9.7%) patients developed DHF in the treatment arm compared to 22 (17.5%) who were on the placebo although this was not significant (p = 0.09, relative risk 0.68, 95% CI 0.41 to 1.08). Rupatadine also significantly reduced (p = 0.01) the proportion of patients with platelet counts <50,000 cells/mm3 and significantly reduced (p = 0.04) persisting vomiting, headache and hepatic tenderness (p<0.0001) in patients. There was a significant difference in the duration of illness (p = 0.0002) although the proportion of individuals who required hospital admission in both treatment arms. Only 2 patients on rupatadine and 3 patients on the placebo developed shock, while bleeding manifestations were seen in 6 patients on rupatadine and 7 patients on the placebo.<h4>Conclusions</h4>Rupatadine appeared to be safe and well tolerated and showed a trend towards a reducing proportion of patients with acute dengue who developed DHF. Its usefulness when used in combination with other treatment modalities should be explored.<h4>Trial registration</h4>International Clinical Trials Registration Platform: SLCTR/2017/024.https://doi.org/10.1371/journal.pntd.0010123 |
| spellingShingle | Gathsaurie Neelika Malavige Chandima Jeewandara Ananda Wijewickrama Dumni Gunasinghe Sameera D Mahapatuna Chathurika Gangani Vimalahan Vimalachandran Geethal Jayarathna Yashoda Perera Chandanie Wanigatunga Harsha Dissanayake Shamini Prathapan Eranga Narangoda Damayanthi Idampitiya Laksiri Gomes Samurdhi Wickramanayake Pramodth Sahabandu Graham S Ogg Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial. PLoS Neglected Tropical Diseases |
| title | Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial. |
| title_full | Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial. |
| title_fullStr | Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial. |
| title_full_unstemmed | Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial. |
| title_short | Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial. |
| title_sort | efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue a randomised double blind placebo controlled trial |
| url | https://doi.org/10.1371/journal.pntd.0010123 |
| work_keys_str_mv | AT gathsaurieneelikamalavige efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT chandimajeewandara efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT anandawijewickrama efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT dumnigunasinghe efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT sameeradmahapatuna efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT chathurikagangani efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT vimalahanvimalachandran efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT geethaljayarathna efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT yashodaperera efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT chandaniewanigatunga efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT harshadissanayake efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT shaminiprathapan efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT eranganarangoda efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT damayanthiidampitiya efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT laksirigomes efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT samurdhiwickramanayake efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT pramodthsahabandu efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial AT grahamsogg efficacyofrupatadineinreducingtheincidenceofdenguehaemorrhagicfeverinpatientswithacutedenguearandomiseddoubleblindplacebocontrolledtrial |