Trial Outcomes & Findings for Defibrotide Therapy for SARS-CoV2 (COVID-19) Acute Respiratory Distress Syndrome (ARDS) (NCT NCT04530604)

Last Updated: 2023-05-09

Results Overview

Major hemorrhagic complications will be based on the International Society on Thrombosis and Haemostasis Bleeding scale. 1. Fatal Bleeding, and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or 3. Bleeding associated with a decline in hemoglobin level of \> 2.0 g/dl, leading to transfusion of two or more units of whole blood or red cells. 4. In addition, symptomatic alveolar hemorrhage, macroscopic hematuria, uncontrolled menorrhagia or epistaxis or bleeding from any wound site would also be considered a major hemorrhagic event.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

14 days

Results posted on

2023-05-09

Participant Flow

Of 13 enrolled, 1 participant was screen failed and did not receive any defibrotide.

Participant milestones

Participant milestones
Measure	Defibrotide Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Overall Study STARTED	12
Overall Study Completed Dosing	10
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Defibrotide Therapy for SARS-CoV2 (COVID-19) Acute Respiratory Distress Syndrome (ARDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Defibrotide n=12 Participants Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Age, Customized 18-29 years	0 Participants n=5 Participants
Age, Customized 30-39 years	2 Participants n=5 Participants
Age, Customized 40-49 years	1 Participants n=5 Participants
Age, Customized 50-59 years	2 Participants n=5 Participants
Age, Customized 60-69 years	4 Participants n=5 Participants
Age, Customized 70-79 years	3 Participants n=5 Participants
Age, Customized >80 years	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	12 Participants n=5 Participants
Prior Therapy Dexamethasone and remdesivir	9 Participants n=5 Participants
Prior Therapy Dexamethasone and remdesivir and tocilizumab	3 Participants n=5 Participants
Pressors	6 Participants n=5 Participants
WHO Ordinal Score at Study Entry WHO score of 4	2 Participants n=5 Participants
WHO Ordinal Score at Study Entry WHO score of 6	4 Participants n=5 Participants
WHO Ordinal Score at Study Entry WHO score of 7	6 Participants n=5 Participants
Onset (time in days from diagnosis of SARS - CoV2 to onset of study therapy	9 days n=5 Participants
FiO2	55 Percent n=5 Participants
D-dimer (mcg/ml)	3.25 mcg/ml n=5 Participants
Platelets (K/microliter)	226 (K/microliter) n=5 Participants
O2 support mechanical ventilation	10 Participants n=5 Participants
O2 support nasal cannula/ mask	2 Participants n=5 Participants
PaO2/FiO2	137 mmHg n=5 Participants
anticoagulant used None	9 Participants n=5 Participants
anticoagulant used Low Molecular weight Heparin	2 Participants n=5 Participants
anticoagulant used Heparin	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 14 days

Outcome measures

Outcome measures
Measure	Defibrotide n=12 Participants Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Number of Major Hemorrhagic Complications Within 14 Days of Initiation of Treatment	0 Participants

SECONDARY outcome

Timeframe: 28 days

Number of patients who are alive at Day 28 after starting treatment.

Outcome measures

Outcome measures
Measure	Defibrotide n=12 Participants Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Overall Survival	10 Participants

SECONDARY outcome

Timeframe: 14 days

Number of patients who are alive at Day 14 after starting treatment.

Outcome measures

Outcome measures
Measure	Defibrotide n=12 Participants Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Overall Survival	11 participants

SECONDARY outcome

Timeframe: 14 days

Day 14 ventilator-free survival will be summarized by the number of patients who are both alive and not using a ventilator at Day 14 after starting treatment.

Outcome measures

Outcome measures
Measure	Defibrotide n=12 Participants Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Ventilator-free Survival	5 Participants

SECONDARY outcome

Timeframe: 14 days

Outcome measures

Outcome measures
Measure	Defibrotide n=12 Participants Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Number of Ventilator Free Days Within 14 Days of Study Entry	0 days Interval 0.0 to 14.0

SECONDARY outcome

Timeframe: up to 14 days

Population: 4 participants had improvement by day 14

Improvement in oxygenation defined as an increase in ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) of 50 (or greater) compared to the nadir of PaO2/FiO2.

Outcome measures

Outcome measures
Measure	Defibrotide n=4 Participants Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
The Time to Improvement in Oxygenation	4 days Interval 2.0 to 6.0

SECONDARY outcome

Timeframe: up to 14 days

Ordinal scale: 1. = Ambulatory, no limitation of activities; 2. = Ambulatory, Activity LImited; 3. = Hospitalized, no oxygen therapy; 4. = Oxygen by mask or nasal cannula; 5. = Non-invasive ventilation or high-flow oxygen (O2); 6. = Intubation/mechanical ventilation; 7. = Intubation/Mechanical ventilation plus one of the following: Pressors, Extracorporeal membrane oxygenation (ECMO) or Dialysis; 8. = Decased/Death Key: For change in ordinal score, negative values represent a decline in WHO score from baseline to day 14 (improvement of condition); positive values represent an increase (worsening of condition).

Outcome measures

Outcome measures
Measure	Defibrotide n=12 Participants Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Mean Change in the WHO COVID-19 Ordinal Scale During Therapy	-1 score on a scale Interval -5.0 to 1.0

Adverse Events

Defibrotide

Serious events: 6 serious events

Other events: 9 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Defibrotide n=12 participants at risk Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Infections and infestations Pulmonary Bacterial Infection	33.3% 4/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Surgical and medical procedures ECMO	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Cardiac disorders Arrhythmia	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Cardiac disorders bleeding/ hemorraghic	16.7% 2/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Infections and infestations Pulmonary fungal infection	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Infections and infestations Pulmonary Bacterial infection	16.7% 2/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Infections and infestations Bacterial Infections (Other)	25.0% 3/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Nervous system disorders Neurologic (Other)	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Skin and subcutaneous tissue disorders Skin (rash)	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Surgical and medical procedures Tracheostomy	16.7% 2/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.

Other adverse events

Other adverse events
Measure	Defibrotide n=12 participants at risk Defibrotide: All patients received 25 milligram/kilogram/day (mg/kg/day) of defibrotide, given in 4 divided doses (approximately every 6 hours), each dose infused over 2-hours intravenously (IV). The planned duration of study therapy was 7 days (while in the hospital), with the following qualifications: * Patients who responded to study therapy prior to day 7 (able to discontinue oxygen) discontinued study therapy at that earlier time point. * Patients who did not respond to study therapy by day 7 of therapy, evidenced by \<20% reduction (or a worsening) of the amount of supplemental oxygen they were receiving, discontinued study therapy at day 7. * Patients who had evidence of a partial pulmonary response by day 7 (\>20% reduction in supplemental oxygen requirement, but still requiring supplemental oxygen) could elect to continue to receive study drug through an additional 7 days of study (total 14-day therapy course).
Blood and lymphatic system disorders Anemia	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Blood and lymphatic system disorders Leukocytosis	25.0% 3/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Cardiac disorders Thrombocytosis	25.0% 3/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Infections and infestations Pulmonary Infections (bacterial)	33.3% 4/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Investigations Hypernatremia	25.0% 3/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Investigations Hyperkalemia	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Investigations Hypercalcemia	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Investigations Increased ALT	25.0% 3/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Investigations Increased AST	25.0% 3/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Investigations Uremia	25.0% 3/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Investigations alkalosis	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Renal and urinary disorders creatinine	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.
Surgical and medical procedures ECMO	8.3% 1/12 • For death and SAEs, participants were followed up at 30 days after completion of therapy; for most participants, 37 days up to a maximum of 44 days. The "other adverse events" table includes any AE (grade 1-5) that occurred during receipt of study drug therapy. Data was collected only during study treatment (7 days for most participants; 14 days for 1). Participants were already hospitalized and extremely sick so SAEs or AEs after treatment was completed are noted by footnote. AEs present at baseline were not recorded as AE, provided there was no clinical worsening of the event during study therapy. Of the 10 out of 12 patients with baseline grade 4 respiratory toxicity, all received mechanical ventilation, and 3 had subsequent progression of respiratory disease and died from progressive respiratory failure after completing study therapy.

Additional Information

Principal Investigator, Dr. Greg Yanik

University of Michigan

Phone: 734 232-9335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place