Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Treatment of Ventricular Tachyarrhythmias Refractory To Shock With Beta Blockers: The SHOCK and BLOCK Trial (Shock n Block)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00401882
Recruitment Status : Terminated (Difficult accrual)
First Posted : November 22, 2006
Results First Posted : March 31, 2017
Last Update Posted : May 25, 2017
Sponsor:
Collaborator:
Medtronic BRC
Information provided by (Responsible Party):
David Haines, MD, William Beaumont Hospitals

Tracking Information
First Submitted Date  ICMJE November 17, 2006
First Posted Date  ICMJE November 22, 2006
Results First Submitted Date  ICMJE July 18, 2013
Results First Posted Date  ICMJE March 31, 2017
Last Update Posted Date May 25, 2017
Study Start Date  ICMJE January 2007
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2017)
Return of Spontaneous Circulation [ Time Frame: After electrical defibrillation ]
The patient will be evaluated for sufficiently stable and organized rhythm and blood pressure.
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2006)
Return of Spontaneous Circulation
Change History Complete list of historical versions of study NCT00401882 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2017)
  • Survival to Hospital Discharge [ Time Frame: from time of arrest to discharge or death ]
    the number of patients who are alive at hospital discharge
  • Adverse Effects [ Time Frame: 30 days ]
  • Number of Precordial Shocks Required After the Administration of Metoprolol or Epinephrine [ Time Frame: 120 minutes ]
  • Total Duration of Resuscitative Efforts [ Time Frame: 120 minutes ]
  • Need for Additional Antiarrhythmic Drugs [ Time Frame: 120 minutes ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2006)
  • Survival to Hospital Discharge
  • Adverse Effects
  • Number of Precordial Shocks Required After the Administration of Metoprolol or Epinephrine
  • Total Duration of Resuscitative Efforts
  • Need for Additional Antiarrhythmic Drugs
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of Ventricular Tachyarrhythmias Refractory To Shock With Beta Blockers: The SHOCK and BLOCK Trial
Official Title  ICMJE Treatment of Ventricular Tachyarrhythmias Refractory To Shock With Beta Blockers: The SHOCK and BLOCK Trial
Brief Summary The purpose of this research study is to evaluate the effectiveness of metoprolol, a "beta blocker," in treating patients in the hospital with a cardiac arrest. It will be given intravenously (given into a vein). The subjects who will take part in this study are 18 years of age or older, are experiencing a cardiac arrest in the hospital, and are in a life threatening situation. Patients who develop a cardiac arrest require prompt electrical defibrillation (electrical shocks) to restore the normal beating rhythm of the heart. In patients who do not respond to electrical defibrillation, current standard of care recommends the use of medications which have been shown to be of unknown benefit. Some people recover from a cardiac arrest, but many people do not. We want to learn whether giving metoprolol will improve survival of patients with a cardiac arrest. A total of 100 patients will be enrolled in the study. Patients will receive either the standard of care with the drug epinephrine or the standard of care plus metoprolol.
Detailed Description

Sudden cardiac death (SCD) is a catastrophic event and most commonly results from acute ventricular tachyarrhythmias (abnormal and lethal heart rhythms). It is often triggered by acute coronary events, which may occur in persons without known cardiac disease or in association with structural heart disease. Advanced therapies such as thrombolytic agents, percutaneous coronary intervention, and implantable cardioverter defibrillators are of no value to thousands of victims who do not survive. Many instances of SCD cannot be predicted and any intervention directed toward the general population would have to be applied to an estimated 1000 persons for every 1 person in whom SCD might be prevented. Thus, it would be reasonable to develop new treatment strategies to improve response to resuscitative efforts.

Prompt electrical defibrillation (electrical shocks) is the treatment of choice in persons who develop SCD due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). However, in up to 25% of all cardiac arrests, patients develop shock resistant VF, defined as VF persisting beyond three defibrillation attempts, and 87-97% of these patients die. Medical therapy, including antiarrhythmic agents, sympathomimetic agents (i.e. stimulants), and buffers have been relegated to a secondary role since there is little evidence that they are of benefit and there use is considered indeterminate or class IIB. Furthermore, the "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care" of the American Heart Association and the International Liaison Committee on Resuscitation recommend antiarrhythmic drugs as "acceptable" and "probably helpful" in the treatment of VF that persists after three or more external defibrillation shocks. It has been previously reported that the survival rate of hospital patients suffering a cardiac arrest in which epinephrine was required was only 6%. Furthermore, Dorian et al reported a survival to hospital admission of 22.8% in patients suffering an out of hospital cardiac arrest and receiving amiodarone. It is believed that the acute effects of amiodarone are due to the class II or beta blocking effects of the drug.

Resuscitation can only be considered successful if the survivor has no disabling cognitive function. The American Heart Association/International Liaison Committee on Resuscitation guidelines state that with a duration of cardiac arrest of > 8 to 10 minutes, the frequency of significant, permanent neurologic damage becomes unacceptably high. Newer treatment modalities are needed to improve patient outcomes.

Epinephrine has been used during cardiopulmonary resuscitation for more than 100 years yet its use has become controversial because it is associated with increased myocardial oxygen consumption, ventricular tachyarrhythmias, and myocardial dysfunction during the period after resuscitation. The current International Guidelines on Emergency Cardiac Care cite both epinephrine and vasopressin as acceptable vasopressor drugs for treatment of refractory VF but neither drug is acknowledged to be of proven benefit.

Beta blockers might improve patient outcomes by blunting the adverse affects of a hyperadrenergic state that occurs during a cardiac arrest and by improving the balance between myocardial oxygen supply and demand. Ditchey et al showed in an animal model that pretreatment with a beta blocker prior to cardiac arrest followed by standard epinephrine therapy results in reduced myocardial injury during CPR without compromising successful defibrillation or post resuscitation left ventricular function.

The current research protocol was formulated in an attempt to develop new treatment options for patients who develop an in-hospital VF or pVT arrest refractory to electrical defibrillation with the specific goal of improving patient outcomes. The trial will utilize pre-filled, blinded syringes of Metoprolol in patients who develop an in-hospital cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia (see study protocol).

Sudden cardiac death (SCD) claims approximately 250,000 persons annually in the United States. Ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) appear to be responsible for 25-35% of all out of hospital episodes of sudden cardiac death. The reported average survival to hospital discharge following in-hospital arrest is just as poor at approximately 14-17% despite the development of widespread implementation of basic and advanced cardiac life support. Current American Heart Association (AHA) guidelines recommend prompt electrical defibrillation to reestablish organized electrical activity. Increasing duration of VF (i.e. "shock resistant VF") can result in two major adverse effects. First, an increased duration can reduce the ability to terminate the arrhythmia8. Second, if VF continues for more than four minutes, there is irreversible damage to the central nervous system and other organs. Despite aggressive efforts, successful resuscitation from out-of-hospital cardiac arrest occurs in only one third of patients and only about 10% of all patients are ultimately discharged from the hospital, many of whom are neurologically impaired. Also, the outcome of patients who suffer an in-hospital cardiac arrest is poor with reported survival to hospital discharge rates of 10-15%. Thus, despite improvements and advances in the treatment of heart disease, the outcome of patients experiencing SCD remains poor.

Prompt and early defibrillation of VF or pVT has become the standard of care. Drug therapy for shock resistant VF or pVT has been relegated to a secondary role since there is little evidence that these agents are of benefit. As a result, their use is considered indeterminate or class IIB. In addition, cardiac arrest and cardiopulmonary resuscitation are extreme forms of stress that lead to the highest catecholamine levels ever recorded in both human or experimental animal models. Endogenous catecholamine concentrations are high during ventricular fibrillation even in the absence of epinephrine administration. Currently, epinephrine is the vasopressor of choice for the treatment of cardiac arrest although vasopressin has been used as an alternative. Of note, vasopressin has been shown to be superior to epinephrine in patients with asystole however, its effects were similar to those of epinephrine in the management of VF or pulseless electrical activity. Furthermore, previous studies have raised concern that epinephrine's beta adrenergic effect may increase the myocardial oxygen consumption of the fibrillating heart and predispose to post-defibrillation dysfunction and cardiac arrhythmias.

Numerous animal studies have shown that beta adrenergic blockade reduces myocardial injury and improves survival. Kudenchuk, et al undertook a study in patients with out of hospital cardiac arrest due to ventricular fibrillation. Patients were randomized to receive either amiodarone or placebo after three consecutive defibrillations and one dose of epinephrine. The authors concluded that patients who received amiodarone had a higher rate of survival to hospital admission. It is felt that the beneficial effects are related to the initial class II or beta blocking properties of amiodarone. Furthermore, Dorian, et al reported a higher rate of survival to hospital admission in patients who received amiodarone as compared to lidocaine for shock resistant out-of-hospital ventricular fibrillation. Analysis from the European Myocardial Infarct Amiodarone Trial and the Canadian Amiodarone Myocardial Infarction Trial revealed an interaction between beta-blockers and amiodarone, specifically, the combination group had a better survival and the interaction was statistically significant for arrhythmic death or resuscitated arrest.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Cardiac Arrest
  • Sudden Cardiac Death
  • Ventricular Fibrillation
  • Tachycardia, Ventricular
Intervention  ICMJE
  • Drug: Epinephrine
    Epinephrine (1 mg) IV additional doses
    Other Name: adrenaline
  • Drug: Metoprolol
    Metoprolol 5 mg IV (up to two times only) instead of epinephrine additional doses
    Other Name: lopressor
Study Arms  ICMJE
  • Active Comparator: Standard Of Care Drug Epinephrine
    Additional doses of Epinephrine (1 mg) given as part of standard of care during cardiac arrest
    Intervention: Drug: Epinephrine
  • Active Comparator: IV Metoprolol instead Epinephrine
    IV metoprolol 5 mg. up to 2 times (only) during cardiac arrest will be given instead of additional Epinephrine doses
    Intervention: Drug: Metoprolol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 13, 2012)
7
Original Enrollment  ICMJE
 (submitted: November 20, 2006)
100
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All patients age > 18 years of age who develop an in-hospital VF or pVT arrest which persists after three or more precordial shocks.
  • Patients who develop an in-hospital cardiac arrest due to asystole or PEA which subsequently converts to VF or pVT will be included.

Exclusion Criteria:

  • Pediatric patients
  • Pregnancy
  • Age < 18 years of age
  • Patients who develop VF or pVT in the emergency room, operating room or surgical intensive care unit.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00401882
Other Study ID Numbers  ICMJE 2006-008
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party David Haines, MD, William Beaumont Hospitals
Study Sponsor  ICMJE David Haines, MD
Collaborators  ICMJE Medtronic BRC
Investigators  ICMJE
Principal Investigator: David E Haines, MD William Beaumont Hospitals
PRS Account William Beaumont Hospitals
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP