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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by University of Washington.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Graham Nichol, University of Washington
ClinicalTrials.gov Identifier:
NCT01509040
First received: January 9, 2012
Last updated: January 11, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Cardiac Arrest
Other: Standard Care
Other: Low Volume Hemofiltration
Other: High Volume Hemofiltration
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Intervention Compliance [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Enrollment [ Designated as safety issue: No ]
    This will be defined as the proportion of eligible patients who are randomized.

  • Clearance of Inflammatory Mediators [ Designated as safety issue: No ]
    Venous blood samples will be obtained periodically after randomization, processed, stored, then tested for serum cytokine levels.

  • Total volume intravenous fluid infused [ Designated as safety issue: No ]
    This will be defined as the volume of fluid (in mL) infused during the first 48 hours from enrollment.

  • Use of pressors and inotropes [ Designated as safety issue: No ]
    This includes use of dopamine, dobutamine, epinephrine, neseritide, norepinephrine, or phenylephrine during the first 48 hours from enrollment.

  • Shock [ Designated as safety issue: No ]
    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.

  • Ejection Fraction [ Designated as safety issue: No ]
    This will be assessed by standard transthoracic echocardiographic methods 48 hours after enrollment in control and intervention patients

  • Number of Hospital Days [ Designated as safety issue: No ]
    This will be described for all hospitalized patients as a measure of morbidity after resuscitation.

  • Time Interval from 911 Call to Patient Death [ Designated as safety issue: No ]
    This will be described for all hospitalized patients as a measure of morbidity after resuscitation.

  • Expected Adverse Event [ Designated as safety issue: Yes ]

    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.


  • Safety Outcome [ Designated as safety issue: Yes ]

    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.


  • Unexpected Adverse Device Events (UADE) [ Designated as safety issue: Yes ]
    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.

  • Clinical Safety Outcomes
    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


Estimated Enrollment: 30
Study Start Date: January 2012
Arms Assigned Interventions
Active Comparator: Control Other: Standard Care

A three-lumen central venous catheter will be inserted for central venous pressure monitoring. All patients shall receive 500-mL bolus of intravenous crystalloid given every 30 minutes to achieve central venous pressure of 8 to 12 mm Hg; vasopressors if mean arterial pressure is less than 65 mm Hg; and vasodilators if mean arterial pressure is 90 mm Hg or above.

Concurrent intervention will include initiation and maintenance of therapeutic hypothermia with a target core temperature of below 34°C via standard external cooling techniques (ArcticSun Temperature Management System, Medivance Inc., Louisville, CO) in all patients.

Percutaneous coronary intervention shall be performed as soon as feasible in those patients who have ST elevation or left bundle branch block on their initial ECG.

Serum biochemistry (including sodium, potassium, bicarbonate, glucose, calcium, phosphate, magnesium and lactate) will be monitored every 6 hours and as required.

Experimental: Low Volume Hemofiltration Other: Standard Care

A three-lumen central venous catheter will be inserted for central venous pressure monitoring. All patients shall receive 500-mL bolus of intravenous crystalloid given every 30 minutes to achieve central venous pressure of 8 to 12 mm Hg; vasopressors if mean arterial pressure is less than 65 mm Hg; and vasodilators if mean arterial pressure is 90 mm Hg or above.

Concurrent intervention will include initiation and maintenance of therapeutic hypothermia with a target core temperature of below 34°C via standard external cooling techniques (ArcticSun Temperature Management System, Medivance Inc., Louisville, CO) in all patients.

Percutaneous coronary intervention shall be performed as soon as feasible in those patients who have ST elevation or left bundle branch block on their initial ECG.

Serum biochemistry (including sodium, potassium, bicarbonate, glucose, calcium, phosphate, magnesium and lactate) will be monitored every 6 hours and as required.

Other: Low Volume Hemofiltration

Patients allocated to standard care plus low-volume HF will receive isovolemic HF using the Prismaflex System (Gambro Renal Inc., Lakewood, CO) 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. We will add 3.1mg/dL phosphate (1.0 mmol/L) to each bag. The replacment fluid will be adjusted as required based on results of the 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 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.

Experimental: High Volume Hemofiltration Other: Standard Care

A three-lumen central venous catheter will be inserted for central venous pressure monitoring. All patients shall receive 500-mL bolus of intravenous crystalloid given every 30 minutes to achieve central venous pressure of 8 to 12 mm Hg; vasopressors if mean arterial pressure is less than 65 mm Hg; and vasodilators if mean arterial pressure is 90 mm Hg or above.

Concurrent intervention will include initiation and maintenance of therapeutic hypothermia with a target core temperature of below 34°C via standard external cooling techniques (ArcticSun Temperature Management System, Medivance Inc., Louisville, CO) in all patients.

Percutaneous coronary intervention shall be performed as soon as feasible in those patients who have ST elevation or left bundle branch block on their initial ECG.

Serum biochemistry (including sodium, potassium, bicarbonate, glucose, calcium, phosphate, magnesium and lactate) will be monitored every 6 hours and as required.

Other: High Volume Hemofiltration
Patients allocated to standard care plus 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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01509040

Contacts
Contact: Graham Nichol, MD MPH nichol@uw.edu
Contact: Deborah Fly, MSN debfly@uw.edu

Locations
United States, Washington
Harborview Medical Center Recruiting
Seattle, Washington, United States, 98040
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Graham Nichol, MD University of Washington
  More Information

No publications provided

Responsible Party: Graham Nichol, Professor, University of Washington
ClinicalTrials.gov Identifier: NCT01509040     History of Changes
Other Study ID Numbers: WASH CARDIAC
Study First Received: January 9, 2012
Last Updated: January 11, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
Resuscitated from Out-of-Hospital Cardiac Arrest

Additional relevant MeSH terms:
Heart Arrest
Out-of-Hospital Cardiac Arrest
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 30, 2014