Washington Study of Hemofiltration After Out-of-Hospital Cardiac Arrest

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the feasibility of hemofiltration in patients resuscitated from cardiac arrest. Cardiac arrest is the loss of mechanical activity of the heart including the loss of detectable pulse, or spontaneous breathing. When heart function is restored, the cells of the body release molecules into the blood that cause inflammation, unstable blood pressure, organ dysfunction and death. Hemofiltration is a technique of washing the blood to remove fluid and molecules from it. Hemofiltration is a proven therapy for renal failure, but is considered investigational for treatment after resuscitation from cardiac arrest. Some experts believe that hemofiltration after heart function is restored can remove inflammation from the blood, maintain blood pressure and organ function. Others believe that intravenous fluid and medications are sufficient to maintain blood pressure and organ function. Since the inflammation that occurs after restoration of heart function lasts, the investigators continue hemofiltration for up to 48 hours. Whether hemofiltration or intravenous fluids and medications is better is not known. The investigators are checking if they can wash the blood of patients resuscitated from cardiac arrest before the investigators can begin a large randomized trial to test whether hemofiltration improves their outcome. The investigators are testing this by randomly allocating patients resuscitated from cardiac arrest to receive low volume hemofiltration, high volume hemofiltration, or intravenous fluids and medications alone. The null hypotheses are that less than 80% of eligible patients will be enrolled, and that less than 80% of enrolled patients will undergo low-volume or high-volume hemofiltration (HF) for at least 80% of 48 hours.

Detailed Description
-----------------
Patients resuscitated from out-of-hospital cardiac arrest will be randomly allocated to one of three groups; Standard of care: Initiate standard of post-resuscitative care including a triple lumen catheter to monitor central venous pressure, core temperature maintenance between 32C and 34C if unconscious. Fluids, inotropes, vasopressors, vasodilators to maintain hemodynamics. Low-volume Hemofiltration for 48 hours: Initiate standard of post-resuscitative care including a triple lumen catheter to monitor central venous pressure, core temperature maintenance between 32C and 34C if unconscious. Hemofiltration x 48 hours via a 11.5F double lumen venous catheter, blood flow 250mL/h, ultrafiltration 45mL/kg/h. Fluids, inotropes, vasopressors, vasodilators to maintain hemodynamics. High-volume Hemofiltration for 48 hours: Initiate standard of post-resuscitative care including a triple lumen catheter to monitor central venous pressure, core temperature maintenance between 32C and 34C if unconscious. Hemofiltration x 48 hours via 11.5F double lumen venous catheter, blood flow 250 mL/h, ultrafiltration 90 mL/kg/h. Fluids, inotropes, vasopressors, vasodilators to maintain hemodynamics. 30 patients will be enrolled.

Official Title
-----------------
Washington Study of Hemofiltration After Out-of-Hospital Cardiac Arrest

Conditions
-----------------
Cardiac Arrest

Intervention / Treatment
-----------------
* Other: Standard Care
* Device: Low Volume Hemofiltration
* Device: High Volume Hemofiltration


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: adults restoration of spontaneous circulation sustained to hospital arrival after OOHCA with any first recorded rhythm aged >=65 years less than 1 h from call to 911 until emergency department arrival less than 6 h from arrival until randomization informed consent provided by legally-authorized representative Exclusion Criteria: do not attempt resuscitation orders; known end-stage terminal illness pre-arrest; major pre-arrest neurological dysfunction; another reason to be comatose (e.g. drug overdose) chronic steroid use non-English speaking LAR previous enrollment in the trial blunt, penetrating, or burn-related injury; exsanguination; drowning, electrocution or strangulation known pregnancy known prisoner weight > 100 kg persistent (i.e. 30 minutes) SBP< 80 mmHg despite pressors; refractory ventricular arrhythmias; severe bradycardia without a pacemaker thrombocytopenia (i.e. < 50,000/microL) or coagulopathy (i.e. INR > 1.5) or inferior vena cava filter in situ known cirrhosis serum ionized calcium < 2.2 mmol/L serum lactate > 6 mmol/L obeying verbal commands

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Initiate standard post-resuscitative care including a triple lumen catheter to monitor central venous pressure, core temperature maintenance between 32C and 34C if unconscious. Fluids, 500-mL bolus of intravenous crystalloid given every 30 minutes to achieve a central venous pressure of 8 to 12 mm Hg; inotropes, vasopressors if mean arterial pressure is less than 65 mm Hg; vasodilators, if mean arterial pressure is 90 mm Hg or above to maintain hemodynamics. | Other: Standard Care<br>* Triple-lumen central venous catheter inserted for pressure monitoring. All patients to receive 500-mL bolus of intravenous crystalloid every 30 minutes to achieve central venous pressure of 8 to 12 mm Hg; vasopressors if mean arterial pressure less than 65 mm Hg; and vasodilators if mean arterial pressure is 90 mm Hg or above. Initiation and maintenance of therapeutic hypothermia, target core temperature of below 34°C via standard external cooling techniques. Percutaneous coronary intervention performed as soon as feasible in patients with ST elevation or left bundle branch block on initial ECG. Serum biochemistry (including sodium, potassium, bicarbonate, glucose, calcium, phosphate, magnesium and lactate) monitored every 6 hours.<br>|
| Experimental: Low Volume Hemofiltration<br>Initiate standard post-resuscitative care including a triple lumen catheter to monitor central venous pressure, core temperature maintenance between 32C and 34C if unconscious. Hemofiltration x 48 hours via 11.5F double lumen venous catheter, blood flow 250 mL/h, ultrafiltration 45 mL/kg/h. Fluids, 500-mL bolus of intravenous crystalloid given every 30 minutes to achieve a central venous pressure of 8 to 12 mm Hg; inotropes, vasopressors if mean arterial pressure is less than 65 mm Hg; vasodilators, if mean arterial pressure is 90 mm Hg or above to maintain hemodynamics. | Other: Standard Care<br>* Triple-lumen central venous catheter inserted for pressure monitoring. All patients to receive 500-mL bolus of intravenous crystalloid every 30 minutes to achieve central venous pressure of 8 to 12 mm Hg; vasopressors if mean arterial pressure less than 65 mm Hg; and vasodilators if mean arterial pressure is 90 mm Hg or above. Initiation and maintenance of therapeutic hypothermia, target core temperature of below 34°C via standard external cooling techniques. Percutaneous coronary intervention performed as soon as feasible in patients with ST elevation or left bundle branch block on initial ECG. Serum biochemistry (including sodium, potassium, bicarbonate, glucose, calcium, phosphate, magnesium and lactate) monitored every 6 hours.<br>Device: Low Volume Hemofiltration<br>* Patients will receive isovolemic HF at a blood flow rate of 250 mL/min and ultrafiltration rate of 45 mL/kg/h for 48 hours. Initial replacement solution will be Prismasol BGK4/2.5. 3.1mg/dL phosphate (1.0 mmol/L) added to each bag. Replacement fluid adjusted as required based on chemistry values for sodium, potassium, bicarbonate, glucose, calcium, phosphate, magnesium and lactate. Vascular access for HF will be via an 11.5-F, double-lumen venous catheter in a central vein. The hemofiltrate will be replaced by fluid infused before (i.e. predilution) and after (i.e. postdilution) the filter. A fixed ratio of 80:20 predilution:postdilution used. HF 1400 (i.e. polysulfone -based membrane) filters used throughout study. Hemofilter changed every 6 h after initiation of HF, and as required.<br>|
| Experimental: High Volume Hemofiltration<br>Initiate standard post-resuscitative care including a triple lumen catheter to monitor central venous pressure, core temperature maintenance between 32C and 34C if unconscious. Hemofiltration x 48 hours via 11.5F double lumen venous catheter, blood flow 250 mL/kg/h, ultrafiltration 90 mL/kg/h. Fluids, 500-mL bolus of intravenous crystalloid given every 30 minutes to achieve a central venous pressure of 8 to 12 mm Hg; inotropes, vasopressors if mean arterial pressure is less than 65 mm Hg; vasodilators, if mean arterial pressure is 90 mm Hg or above to maintain hemodynamics. | Other: Standard Care<br>* Triple-lumen central venous catheter inserted for pressure monitoring. All patients to receive 500-mL bolus of intravenous crystalloid every 30 minutes to achieve central venous pressure of 8 to 12 mm Hg; vasopressors if mean arterial pressure less than 65 mm Hg; and vasodilators if mean arterial pressure is 90 mm Hg or above. Initiation and maintenance of therapeutic hypothermia, target core temperature of below 34°C via standard external cooling techniques. Percutaneous coronary intervention performed as soon as feasible in patients with ST elevation or left bundle branch block on initial ECG. Serum biochemistry (including sodium, potassium, bicarbonate, glucose, calcium, phosphate, magnesium and lactate) monitored every 6 hours.<br>Device: High Volume Hemofiltration<br>* Patients allocated to high volume HF will receive HF at 250 mL/h blood flow rate and 90 mL/kg/h ultrafiltration rate for 48 hours. All other care will be identical to that provided in the low volume HF group. Vascular access for HF will be via an 11.5-F, double-lumen venous catheter in a central vein. The hemofiltrate will be replaced by fluid infused into the bloodstream before (i.e. predilution) and after (i.e. postdilution) the filter. A fixed ratio of 80:20 predilution:postdilution will be used. HF 1400 (i.e. polysulfone -based membrane) filters will be used throughout the study. The hemofilter will be changed every 6 h after initiation of HF, and otherwise as required.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intervention Compliance | Intervention Compliance will be defined as the proportion of intervention patients who are alive and undergo hemofiltration (HF) for at least 80% of 48 hours from randomization. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enrollment | This will be defined as the proportion of eligible patients who are randomized. | 12 hours | 
| Clearance of Inflammatory Mediators | Venous blood samples will be obtained periodically after randomization, processed, stored, then tested for serum cytokine levels. | 48 hours | 
| Total Volume Intravenous Fluid Infused | This will be defined as the volume of fluid (in mL) infused during the first 48 hours from enrollment. | 48 hours | 
| Use of Pressors and Inotropes | This includes use of dopamine, dobutamine, epinephrine, nesiritide, norepinephrine, or phenylephrine during the first 48 hours from enrollment. | 48 hours | 
| Shock | This will be defined as systolic blood pressure < 65 at the end of any four hour period during the initial 48 hours of enrollment in control and intervention patients. | 48 hours | 
| Ejection Fraction | This will be assessed by standard transthoracic echocardiographic methods 48 hours after enrollment in control and intervention patients | 48 hours | 
| Number of Hospital Days | This will be described for all hospitalized patients as a measure of morbidity after resuscitation. | 6 months | 
| Time Interval From 911 Call to Patient Death | This will be described for all hospitalized patients as a measure of morbidity after resuscitation. | 1 year | 
| Expected Adverse Event | Device-Related Hematoma at insertion site, vessel perforation, wound infection, deep venous thrombosis or pulmonary embolism. Device Failure Mechanical failure Hypertension- SBP>160 mmHg, or DBP >120 mmHg. Hypotension- SBP<60 mmHg. Hypervolemia- CVP > 12 cm. Hypovolemia- CVP < 2 cm. Hypokalemia- serum potassium concentration < 3.5 mmol/L. Alkalosis- serum bicarbonate > 32 mmol/L. Hyperglycemia- serum glucose > 240 mg/dL. Hypophosphatemia- serum phosphate concentration < 0.8 mmol/L. Hypocalcemia- serum ionized calcium < 2.2 mmol/L. Lactic acidosis- serum lactate > 6 mmol/L. | 48 hours | 
| Safety Outcome, Number of Participants With STEMI, Radiographic Pulmonary Edema, or Arrhythmia | ST-Elevation Myocardial Infarction- ECG criteria and biomarker criteria for acute infarction. Radiographic Pulmonary Edema- radiographic presence of alveolar or interstitial edema, bilateral pleural effusions, cardiomegaly or venous congestion. Arrhythmia- other than sinus rhythm observed after randomization. Arrhythmia requiring treatment- rhythm with subsequent use of an antiarrhythmic drug or electrical therapy observed after randomization. Arrhythmia with cardiovascular instability- any rhythm with cardiovascular instability as determined by the DSMB, observed after randomization. | 48 hours | 
| Unexpected Adverse Device Events (UADE) | These will be defined as any unexpected adverse effect on health or safety or any unexpected life-threatening problem caused by, or associated with, a device, if that effect or problem was not previously identified in nature, severity, or degree of incidence in this investigation plan or application which will be submitted to the Food and Drug Administration (including a supplementary plan or application), or any other unexpected serious problem associated with a device. The death or neurological impairment of an individual patient will not be considered an adverse event in this study. | 48 hours | 
| Clinical Safety Outcomes; Number of Participants With Clinical Diagnoses | Clinical diagnoses of cerebral bleeding, stroke, bleeding requiring transfusion or surgical intervention, rearrest, pulmonary edema, rib or sternal fractures, internal thoracic or abdominal injuries as noted in the discharge summary | Discharge | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Resuscitated from Out-of-Hospital Cardiac Arrest