DEFINE [COVID-19] [UPH]
Research type
Research Study
Full title
Rapid Experimental Medicine for COVID-19
IRAS ID
282934
Contact name
Kevin Dhaliwal
Contact email
Sponsor organisation
University of Edinburgh
Eudract number
2020-002230-32
ISRCTN Number
ISRCTN14212905
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
The purpose of this programme of trials is to evaluate the safety of treatments that are already used in patients for other diseases for use as treatments for patients with COVID-19. Safety will be assessed using blood tests, physical examination, blood pressure/heart rate/temperature and respiratory rate, daily electrocardiogram (ECG) to check how the heart is working, and adverse events. The results of these studies will support further national and international trials. The main aim is to prevent the lung damage in patients with COVID-19 that leads to respiratory failure. This programme will be comprised of small studies and will focus on how effective the treatments are, as well as their impact on inflammation in the body. The design of the trials will be changed as needed to support the further development of possible treatments for COVID-19 patients. \nPatients will be randomly given:\n•\tNafamostat with standard hospital treatment \n•\tTD139 with standard hospital treatment \n•\tStandard hospital treatment\nBoth Nafamostat and TD139 have been used in patients before and it is hoped they will reduce the effect of COVID-19. Nafamostat inhibits an enzyme in the body serine protease inhibitor and is routinely used to treat patients with a blood clotting disorder. It is given as a continuous infusion through a drip for 7 days. TD139 has been tested in healthy volunteers and patients with a type of lung disease that results in scarring of the lungs. It is given as an inhaler once or twice a day for 14 days. Information on the patient’s condition will be collected throughout the study.
Lay summary of study results:
Adults, in hospital with COVID-19, who had evidence of pneumonitis on their chest x-ray, and required oxygen therapy were eligible to be recruited to the study, and if recruited, randomised to receive standard care only (SOC), or SOC plus inhaled GB0139 (Appendix 1) or SOC plus an intravenous infusion of Nafamostat mesylate. Below are the summary of results for each appendix/intervention.Appendix 1 Summary:
A total of 20 participants were recruited and randomised to receive SOC and inhaled GB0139. It was found that inhaled GB0139 was well tolerated and no treatment related serious adverse events were reported. Within the treatment group, 40 adverse events were reported, with a similar number reported in the SOC only group (35 events reported). The results also showed that clinically relevant plasma concentration levels were detected with a reduction in plasma levels of biomarkers associated with inflammation, coagulopathy, major organ function and fibrosis, all showing a downward trend when compared with the results of the SOC only group. The results indicate the therapeutic potential for inhaled GB0139 in hospitalised patients with COVID-19.
Full details available at: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fdoi.org%252F10.1101%252F2021.12.21.21267983%2FNBTI%2FbB-GAQ%2FAQ%2Fbeb490bf-2844-434d-ba20-441563f7033c%2F2%2F5-a8BI3lPX&data=05%7C02%7Capprovals%40hra.nhs.uk%7Cfc2def145bdc44e7b94e08decd4b60b5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639173920811055064%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=NGn3iDZAM8GnWtkgaDjMpJ8ZgXz8M8MivmwQgf6oewo%3D&reserved=0Appendix 2 Summary:
A total of 21 participants were recruited and randomised to receive SOC and intravenous nafamostat.In the nafamostat treatment group, 86% experienced at least one adverse event compared to only 57% of the SOC group. From these results, it was concluded that the nafamostat group were significantly more likely to experience at least one AE and developed significantly higher plasma creatinine levels.
Participants in the nafamostat group, on average, had a longer hospital stay alongside a lower rate of oxygen free days. There were no other statistically significant differences in endpoints between nafamostat and SOC. Pharmacokinetic data demonstrated that intravenous nafamostat was rapidly broken down to inactive metabolites. We observed no significant anticoagulant effects in thromboelastometry.In conclusion, in hospitalised patients with COVID-19, we did not observe evidence of anti-inflammatory, anticoagulant or antiviral activity with intravenous nafamostat, but did see an increased adverse event rate in this group, when compared with the SOC group.
Full details available at: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fdoi.org%252F10.1016%252Fj.ebiom.2022.103856%2FNBTI%2FbB-GAQ%2FAQ%2Fbeb490bf-2844-434d-ba20-441563f7033c%2F3%2FZL8FzU1Vx9&data=05%7C02%7Capprovals%40hra.nhs.uk%7Cfc2def145bdc44e7b94e08decd4b60b5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639173920811065622%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=wESSJyoz5KW0hh2Preu2NIevfImD7dhW6zMKqUBo4f4%3D&reserved=0
Appendix 3 - this part of the project did not recruit to target and no formal analysis of results could be published. Instead, a brief summary is available at https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.isrctn.com%252FISRCTN14212905%2FNBTI%2FbB-GAQ%2FAQ%2Fbeb490bf-2844-434d-ba20-441563f7033c%2F1%2Fdyw4xgvLzo&data=05%7C02%7Capprovals%40hra.nhs.uk%7Cfc2def145bdc44e7b94e08decd4b60b5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639173920811075880%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=e%2Fiq5YUJAuaDhqvF8mf3PdgiaNauPsljgG%2BQYMD%2FNiA%3D&reserved=0
REC name
Scotland A: Adults with Incapacity only
REC reference
20/SS/0066
Date of REC Opinion
23 Jun 2020
REC opinion
Further Information Favourable Opinion