DEFINE - Evaluating Therapies for COVID-19 (DEFINE)
COVID-19
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
Inclusion Criteria:
- Provision of informed consent from the patient or representative
- Aged at least 16 years
- If the patient is of child bearing potential, the patient, and their partner(s), agree to use medically-accepted double-barrier methods of contraception (eg, barrier methods, including male condom, female condom or diaphragm with spermicidal gel) during the study (if randomised to a treatment arm) and for at least 90 days after termination of study therapy. A vasectomised partner would be considered an appropriate birth control method provided that the partner is the sole male sexual partner and the absence of sperm has been confirmed.
- COVID-19 positive
Exclusion Criteria:
- Current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled cardiac disease (NYHA class IV), uncontrolled renal disease (eGFR <30 mL/min/1.73 m2), severe liver dysfunction (ALT/AST >5x ULN) or bone marrow failure (Hb <80 g/L AND ANC<0.5 mm3 AND platelet count <50,000 uL)
- Women who are pregnant or breastfeeding.
- Participation in another clinical trial of an investigational medicinal product (CTIMP)
- Known hypersensitivity to the IMP or excipients (e.g. lactose)
- Pre-existing or Cconcomittant use of off-label treatments for COVID-19 that are not recognised as locally approved standard care.
- Significant electrolyte disturbance (hyperkalaemia potassium >5.0 mmol/L or hyponatraemia sodium < 120mmol/L)
- Patient currently receiving potassium sparing diuretics that cannot be reasonably withheld
- Patient currently receiving prophylactic or therapeutic anticoagulantsanticoagulation or antiplatelet agents that cannot be reasonably withheld if randomised to Nafamostat
- Patients (or their partners) planning on donating sperm/eggs during the trial period
- Ongoing dialysis
- History of serious liver disease (Child Pugh score > 10)
- Hemoglobin < 80 g/L
- Any known allergy to the IMP/excipients
- Severe uncontrolled diabetes mellitus
- In the Investigator's opinion, patient is unwilling or unable to comply with drug administration plan, laboratory tests or other study procedures.
Sites / Locations
- NHS LothianRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Nafamostat
TD139
Standard of Care
It is intended that the licensed dose (0.2mg/kg/hr) in Japan will be used. Patients randomised to Nafamostat will receive a continuous intravenous infusion at 0.2 mg/kg/hr for 7 days. If a participant is discharged from hospital or can no longer receive this treatment, the treatment will be stopped.
Patients will inhale 5mg x 2 (10 mg) twice daily for the first 48 hrs and then subsequently 5mg x 2 (10 mg) once daily for the remaining 12 days. Unless a participant is discharged from hospital or can no longer use an inhaler - in which case treatment will be stopped at such time. CE marked inhalers will be provided by the Manufacturer. All patients will receive guidance on how to use the inhaler by an appropriately trained member of the research team. Two individual inhalers will be used by each patient over the course of the 14 day study period (each inhaler will be used by one patient for 7 days) and will be thoroughly cleaned with an antiseptic wipe before and after each use.
All treatment arms will be compared to the Standard of Care arm.