Heparin Anticoagulation to Improve Outcomes in Septic Shock: The HALO Pilot

This is an interventional treatment trial for Septic Shock Read More

Inclusion Criteria:

1. ≥ 18 years of age
2. Refractory hypotension documented within 36 hours prior to enrolment that requires institution and ongoing use of vasopressor agents (phenylephrine, norepinephrine, vasopressin, epinephrine, or dopamine > 5 mcg/kg/min) at the time of enrolment. Refractory hypotension is defined as a systolic blood pressure < 90 mmHG or a systolic blood pressure more than 30 mmHg below baseline, or a mean arterial pressure less than 65 mmHG and receipt of greater than or equal to 2 litres of intravenous fluid for the treatment of hypotension.

3. At least 1 other new organ dysfunction defined by the following:

   • Creatinine ≥ 150 µmol/L, or ≥ 1.5x the upper limit of normal or the known baseline creatinine, or < 0.5 ml/kg or urine output for 2 hours(Patients on chronic hemodialysis or peritoneal dialysis must meet one of the following criteria)
   • Need for invasive mechanical ventilation or a P/F ratio < 250
   • Platelets < 100 x109/L, or a drop of 50 x109/L in the 3 days prior to enrollment
   • Arterial pH < 7.30 or base deficit > 5 mmol/L in association with a lactate >/= to 3.0 mmol/L

Exclusion Criteria:

1. Consent declined
2. Clinically apparent other forms of shock including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponnade, tension pneumothorax), hemorrhagic, neurogenic, or anaphylactic
3. Received vasopressor therapy for greater than 36 hours prior to enrollment

4. Have a significant risk of bleeding as evidenced by one of the following:

   • Clinical: Surgery requiring general or spinal anesthesia within 24 hours prior to enrollment, or the potential need for such surgery in the next 24 hours; evidence of active bleeding; a history of severe head trauma requiring hospitalization; intracranial surgery, or stroke within 3 months before the study or any history of intracerebral arteriovenous malformation, cerebral aneurysm, or mass lesions of the central nervous system; a history of congenital bleeding diatheses; gastrointestinal bleeding within 6 weeks before the study unless corrective surgery had been performed; trauma considered to increase the risk of bleeding; presence of an epidural catheter
   • Laboratory: Platelet count < 30 x109/L, INR > 2.0, or baseline aPTT > 50 sec prior to enrollment.
5. Have an indication for therapeutic anticoagulation (e.g. ACS, acute VTE, mechanical valve, etc)
6. Intent of the most responsible physician to prescribe rhAPC
7. Have had a known or suspected adverse reaction to UFH including HIT
8. Are currently enrolled in related trial
9. Known or suspected cirrhosis, or chronic ascites
10. Use of any of the following medications or treatment regimens: unfractionated heparin to treat an active thrombotic event within 12 hours before the infusion enrollment; low-molecular-weight heparin at a higher dose than recommended for prophylactic use (as specified in the package insert) within 12 hours before the infusion; warfarin (if used within 7 days before study entry AND if the INR time exceeded the upper limit of the normal range for the institution); thrombolytic therapy within 3 days before the study, glycoprotein IIb/IIIa antagonists within 7 days before study entry; protein C or rhAPC within 24 hours before enrollment.
11. Terminal illness with a life expectancy of less than 3 months
12. Are pregnant