Heparin Anticoagulation in Septic Shock

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is a pragmatic open-label international randomized trial comparing therapeutic dose intravenous unfractionated heparin (UFH) to standard care venous thromboprophylaxis in patients diagnosed with septic shock.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Manitoba
• Collaborators: Canadian Institutes of Health Research (CIHR); CancerCare Manitoba
• Treatments: Calcium heparin; Heparin

Criteria

Inclusion Criteria:

• ≥ 18 years of age

• Refractory hypotension documented within 18 hours prior to enrolment that requires the institution and ongoing use of vasopressor agents, (phenylephrine, norepinephrine, vasopressin, epinephrine, midodrine or dopamine >5 mcg/kg/min) at the time of enrolment. Refractory hypotension is defined as a systolic blood pressure (SBP) less than 90 mm Hg, or a systolic blood pressure more than 30 mm Hg below baseline, or a mean arterial pressure (MAP) less than 65 mm Hg and receipt of ≥ 2 litres of intravenous fluid for the treatment of hypotension (≥ 1 litre if dialysis dependent end-stage renal disease or if the patient is felt to be in congestive heart failure).

• At least 1 other new organ dysfunction (in addition to refractory hypotension), defined by the following:

1. Creatinine ≥1.5x the known baseline creatinine, or ≥ 26.5 µmol/L increase or <0.5 mL/kg of urine output for 6-12 hours according to the KDIGO [Kidney Disease improving Global Outcomes (KDiGO)] guideline definition of acute kidney injury.

2. Need for invasive mechanical ventilation or a P/F ratio <250

3. Platelets <100 x109/L, or a drop of 50 x109/L in the 3 days prior to enrolment

4. Arterial pH < 7.30 or base deficit > 5 mmol/L in association with a lactate > 4.0 mmol/L

Exclusion Criteria:

• Other forms of shock including cardiogenic, hemorrhagic, hypovolemic, neurogenic, or obstructive shock.

• Clinical suspicion or confirmation of a viral hemorrhagic shock syndrome including, but not limited to, dengue fever

• Rapid clinical improvement; vasopressors likely to be discontinued in the next 6 hours

• Received vasopressor therapy for greater than 18 hours prior to enrolment

• Bleeding Risk:

1. Clinical: Active bleeding; head trauma; intracranial surgery or stroke within 3 months; history of intracerebral arteriovenous malformation, cerebral aneurysm or mass lesions of the central nervous system; history of a bleeding diatheses; gastrointestinal bleeding within 6 weeks; presence of an epidural or spinal catheter; selected cases of recent surgery where IV therapeutic UFH is considered contraindicated

2. Laboratory: Platelet count <50 x109/L, INR >2.0, or baseline aPTT >50 seconds prior to enrolment

• Known or suspected adverse reaction to UFH including heparin induced thrombocytopenia (HIT).

• Use of any of the following treatments: UFH to treat a thrombotic event within 12 hours before enrolment; LMWH at a higher dose than recommended for prophylactic use within 12 hours before the infusion; warfarin (if used within 7 days before study entry AND if the INR exceeds 2.0 at enrolment); thrombolytic therapy within 3 previous days; use of IIb/IIIa inhibitors within the previous 7 days.

• Need for therapeutic anticoagulation

• Terminal illness with a life expectancy of less than 3 months, or no commitment to aggressive care.

• Consent declined from patient or authorized 3rd party

• Physician refusal