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

Cardiac Arrest Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01509040
• Other study ID #: WASH CARDIAC
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 9, 2012
• Last updated: June 8, 2016
• Start date: January 2012
• Est. completion date: June 2014

Study information

• Verified date: June 2016
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: June 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Out-of-Hospital Cardiac Arrest

Intervention

Other:
• Standard Care
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.

Device:
• Low Volume Hemofiltration
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.
• High Volume Hemofiltration
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.

Locations

Country	Name	City	State
United States	Harborview Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Enrollment	This will be defined as the proportion of eligible patients who are randomized.	12 hours	No
Secondary	Clearance of Inflammatory Mediators	Venous blood samples will be obtained periodically after randomization, processed, stored, then tested for serum cytokine levels.	48 hours	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Ejection Fraction	This will be assessed by standard transthoracic echocardiographic methods 48 hours after enrollment in control and intervention patients	48 hours	No
Secondary	Number of Hospital Days	This will be described for all hospitalized patients as a measure of morbidity after resuscitation.	6 months	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes