Patients With COVID-19 Pneumonia Will Allow to Detect an Absolute Reduction in the Rate of Respiratory-failure Clinical Trial
— DEFI-VID19Official title:
Use of Defibrotide to Reduce Progression of Acute Respiratory Failure Rate in Patients With COVID-19 Pneumonia
Verified date | July 2022 |
Source | IRCCS San Raffaele |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Phase II, prospective, interventional, single-arm, multicentric, open label trial, with a parallel retrospective collection of data on not treated patients from IRCCS, San Raffaele Scientific Institute included in the institutional observational study. A sample of 50 patients with COVID-19 pneumonia will allow to detect an absolute reduction in the rate of Respiratory-failure at day+14 after treatment of 20%, assuming that the actual rate of failure in the corresponding not treated patients is 70% (alpha=5%, power=90%, two-sided test). The software PASS15 was used for calculations. The study will also include a parallel retrospective group of temporally concomitant patients from IRCCS, San Raffaele Scientific Institute, who did not receive an experimental treatment and who are enrolled in an already IRB approved observational study
Status | Completed |
Enrollment | 50 |
Est. completion date | May 28, 2021 |
Est. primary completion date | April 7, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Documented COVID-19 pneumonia: defined as upper respiratory tract specimen (nasopharyngeal swab (NPS) or viral throat swab) positive for COVID-19 and/or imaging at computed tomography scan suggestive of COVID-19 pneumonia - Oxygen saturation (SaO2) of 92% or less without oxygen support, or reduction of 3% from basal value of SaO2, or a ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) (PaO2/FiO2) below 300. - Any gender - Age >= 18 years - Written informed consent or as per Ethical Committee indication in case of patients not able to express written informed consent Exclusion Criteria: - Onset of COVID-19 pneumonia >14 days - Orotracheal intubation - Uncontrolled systemic infection (other than COVID-19) - Concomitant use of thrombolytic therapy Concomitant systemic anticoagulant therapy (e.g. heparin, warfarin, direct thrombin inhibitors and direct factor Xa inhibitors) - Haemodynamic instability, defined as inability to maintain mean arterial pressure with single pressor support - Hypersensitivity to the active substance or to any of the excipients of the experimental drug - Patients who, based on the investigator's clinical judgement, are not able to receive the treatment - Pregnancy or breastfeeding patient |
Country | Name | City | State |
---|---|---|---|
Italy | Ospedale San Raffaele | Milano | Lombardia |
Lead Sponsor | Collaborator |
---|---|
IRCCS San Raffaele |
Italy,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | to able to reduce the progression of acute respiratory failure | To demonstrate that the treatment with Defibrotide administered intravenously in addition to the best available therapy according to institutional guidelines (protease inhibitors antiviral treatment and hydroxychloroquine (HCQ), and if needed, metilprednisolone is able to reduce the progression of acute respiratory failure, the need of mechanical ventilation, the transfer to the intensive care unit or death, in patients with severe COVID-19 pneumonia. Patients with a baseline PaO2/FiO2 >= 200: progression of respiratory failure is defined by: severe gas transfer deficit (PaO2/FiO2 < 200); persistent respiratory distress while receiving oxygen (persistent marked dyspnea, use of accessory respiratory muscles, paradoxical respiratory movements); transfer to the intensive care unit; death. The rate will be calculated as the proportion of patients who experienced at least one of the events above by day+14 from treatment start. |
14 days | |
Secondary | Adverse events | To evaluate the safety of Defibrotide will be analyzed the frequency and incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | 7 days | |
Secondary | duration of hospitalization | evaluate the time of hospitalization that will determine how much and how the administration of defibrotide can resolve the infection | 14 days | |
Secondary | systemic inflammation | To evaluate the level of PCR, LDH, ferritin, IL-10, IL-6, TNF-alpha, IFN-gamma, PTX3 at day +7 and +14 after start of treatment with Defibrotide. performed per day. Laboratory values performed at day 7 and 14 will be analyzed and compared with each other to understand their progress. |
14 days | |
Secondary | overall survival | To evaluate the overall survival at day+28 after start treatment with Defibrotide | 28 days |