None listed
Conditions
Brief summary
The pathophysiology of ARDS and sepsis involves a dysregulated response of the immune system to infection. NET-associated proteins, particularly histones play very important role and cause significant tissue damage, which correlate highly with death as an outcome. Our hypothesis is to use STC3141 to neutralize the extracellular histone/NETs. Continuous infusion STC3141 up to 5 days while the patients are on ventilators in ICU compare to standard care.
Interventions
This is a two- stage study.
Stage 1: Patients will receive STC3141 60 mg/hr as an initial infusion rate which was based on phase Ia study in health volunteer and 60mg/hr is the dosage in long term infusion in phase Ia without aPTT increase, followed by a dose increase of 10 mg/hr every 6 hours until the max infusion rate is 100 mg/hr or the aPTT reaches 1.5 x ULN which ever comes first, then the infusion rate will be fixed in the rest of time. The infusion will continue at this rate for 72 hr
This is a two- stage study. Stage 1: Patients will receive STC3141 60 mg/hr as an initial infusion rate which was based on phase Ia study in health volunteer and 60mg/hr is the dosage in long term infusion in phase Ia without aPTT increase, followed by a dose increase of 10 mg/hr every 6 hours until the max infusion rate is 100 mg/hr or the aPTT reaches 1.5 x ULN which ever comes first, then the infusion rate will be fixed in the rest of time. The infusion will continue at this rate for 72 hr. Stage 2: Arm 1 will receive STC3141 with the initial infusion rate decided from Stage 1 by DSMB, the dosage will be adjusted every 6 hours according to subjects’ aPTT as same as stage 1. The target aPTT and Maximum dosage will be based on DSMB recommendation based on data from stage 1. The infusion last up to 120 hours, unless the patients is well enough to be discharged from ICU, or pass away or experienced intolerable adverse event etc.
Sponsors
Grand Medical Pty Ltd
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Subjects entering the ICU and presenting with confirmed or suspected COVID-19-related ARDS will be enrolled in the trial. 1. Aged 18 to 80 years (inclusive at the time of consent) 2. Subjects are diagnosed with moderate to severe ARDS that has been present for less than 3 days 3. Meet Berlin Definition 1) Must have a partial pressure of arterial O2 (PaO2)/ fraction of inspired O2 (FiO2) less than or equal to 200 mmHg on invasive or non-invasive ventilation with the level of positive end-expiratory pressure (PEEP) or continuous positive pressure (CPAP) greater than or equal to 5cmH2O. 2) Bilateral opacities not fully explained by effusion, lobar or lung collapse, or nodules by chest X-ray or CT 3) Respiratory failure not fully explained by heart failure or fluid overload In the opinion of the treating clinicians, likely to survive beyond the day after tomorrow. 4. Subjects who are consented
Exclusion criteria
1. Subjects who have <55 ml/min/BSA 2. Subjects who require ECMO 3. Subjects who require a therapeutic dose of heparin or who are receiving oral anticoagulants, or received warfarin, factor Xa inhibitors within last 24 hours 4. Subjects who have Absolute Neutrophil Count (ANC) <1000/mL; 6. Subjects who have activated Partial Thromboplastin Time (aPTT) >55 s; 7. Severe anaemia (haemoglobin; 8. Bleeding in the past 24 hours requiring blood transfusion; 9. Subjects who have the following chronic organ dysfunction or immunosuppression
Outcome results
None listed