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

• Sponsor: David Haines, MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00401882
• Collaborator: Medtronic BRC (Industry)
• Enrollment: 7
• Location: 1
• Arms: 2
• Duration (Months): 62
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrest; Sudden Cardiac Death; Ventricular Fibrillation; Tachycardia, Ventricular	Drug: Epinephrine; Drug: Metoprolol	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment of Ventricular Tachyarrhythmias Refractory To Shock With Beta Blockers: The SHOCK and BLOCK Trial
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard Of Care Drug Epinephrine Additional doses of Epinephrine (1 mg) given as part of standard of care during cardiac arrest	Drug: Epinephrine; Epinephrine (1 mg) IV additional doses; Other Names: adrenaline
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	Drug: Metoprolol; Metoprolol 5 mg IV (up to two times only) instead of epinephrine additional doses; Other Names: lopressor

Outcome Measures

Primary Outcome Measures

1. Return of Spontaneous Circulation [After electrical defibrillation]

   The patient will be evaluated for sufficiently stable and organized rhythm and blood pressure.

Secondary Outcome Measures

1. Survival to Hospital Discharge [from time of arrest to discharge or death]

   the number of patients who are alive at hospital discharge

2. Adverse Effects [30 days]

3. Number of Precordial Shocks Required After the Administration of Metoprolol or Epinephrine [120 minutes]

4. Total Duration of Resuscitative Efforts [120 minutes]

5. Need for Additional Antiarrhythmic Drugs [120 minutes]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	William Beaumont Hospital	Royal Oak	Michigan	United States	48073

Sponsors and Collaborators

• David Haines, MD
• Medtronic BRC

Investigators

• Principal Investigator: David E Haines, MD, William Beaumont Hospitals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David Haines, MD, Coordinator, William Beaumont Hospitals
• ClinicalTrials.gov Identifier: NCT00401882
• Other Study ID Numbers: 2006-008
• First Posted: Nov 22, 2006
• Last Update Posted: May 25, 2017
• Last Verified: Mar 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by David Haines, MD, Coordinator, William Beaumont Hospitals: Cardiac arrest; Sudden Cardiac Death; Ventricular Fibrillation; Pulseless Ventricular Tachycardia; Cardiopulmonary resuscitation
• Additional relevant MeSH terms: Heart Arrest; Tachycardia; Death, Sudden, Cardiac; Ventricular Fibrillation; Tachycardia, Ventricular; Death; Metoprolol; Epinephrine

Study Results

Participant Flow

Recruitment Details	Patients in the ventricular tacchycardia refractory to shock with beta blocker
Pre-assignment Detail	After the patient was refractory to treatment of the Epinephrine the patient would receive medication called Metroprolol

Arm/Group Title	Additional Doses of Epinephrine	Metoprolol Instead of Additional Epinephrine Doses
Arm/Group Description	Epinephrine: additional doses Epinephrine (1 mg) IV given as part of standard of care in cardiac arrest	Metoprolol: Metoprolol 5 mg IV (up to two times) instead of additional doses of epinephrine
Period Title: Overall Study
STARTED	2	5
COMPLETED	2	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Additional Epinephrine Doses	Metoprolol	Total
Arm/Group Description	Additional Epinephrine (1 mg) IV doses as part of standard of care in cardiac arrest	Metoprolol 5 mg IV (up to two doses only) instead of additional epinephrine doses in cardiac arrest	Total of all reporting groups
Overall Participants	2	5	7
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 50%	4 80%	5 71.4%
>=65 years	1 50%	1 20%	2 28.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.5 (21.9)	60.8 (5.49)	63 (10.69)
Sex: Female, Male (Count of Participants)
Female	1 50%	1 20%	2 28.6%
Male	1 50%	4 80%	5 71.4%
Region of Enrollment (participants) [Number]
United States	2 100%	5 100%	7 100%

Outcome Measures

1. Primary Outcome

Title	Return of Spontaneous Circulation
Description	The patient will be evaluated for sufficiently stable and organized rhythm and blood pressure.
Time Frame	After electrical defibrillation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Additional Doses of Epinephrine	Metoprolol Instead of Additional Epinephrine Doses
Arm/Group Description	Epinephrine: Additional doses of epinephrine (1 mg IV) given as part of standard of care during cardiac arrest	Metoprolol 5 mg IV (up to 2 times) instead of additional epinephrine doses
Measure Participants	2	5
Count of Participants [Participants]	0 0%	1 20%

2. Secondary Outcome

Title	Survival to Hospital Discharge
Description	the number of patients who are alive at hospital discharge
Time Frame	from time of arrest to discharge or death

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Additional Epinephrine Doses	Metoprolol Instead of Additional Epinephrine Doses
Arm/Group Description	Additional doses of Epinephrine (1 mg) given as part of standard of care during cardiac arrest Epinephrine: Epinephrine (1 mg) IV additional doses	IV metoprolol 5 mg. (up to 2 times only) during cardiac arrest will be given instead of additional Epinephrine doses Metoprolol: Metoprolol 5 mg IV (up to two times only) instead of epinephrine additional doses
Measure Participants	2	5
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Adverse Effects
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Additional Doses of Epinephrine	Metoprolol Instead of Additional Epinephrine Doses
Arm/Group Description	Epinephrine: Additional doses of epinephrine IV (1 mg) given as part of standard of care in cardiac arrest	Metoprolol: Metoprolol 5mg IV (up to two times only) instead of additional epinephrine doses
Measure Participants	2	5
Count of Participants [Participants]	0 0%	0 0%

4. Secondary Outcome

Title	Number of Precordial Shocks Required After the Administration of Metoprolol or Epinephrine
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

Data point not analyzed

Arm/Group Title	Additional Epinephrine Doses	Metoprolol
Arm/Group Description	Additional Epinephrine (1 mg) IV doses as part of standard of care in cardiac arrest	Metoprolol 5 mg IV (up to two doses only) instead of additional epinephrine doses in cardiac arrest
Measure Participants	0	0

5. Secondary Outcome

Title	Total Duration of Resuscitative Efforts
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

Data point not analyzed

Arm/Group Title	Additional Epinephrine Doses	Metoprolol
Arm/Group Description	Additional Epinephrine (1 mg) IV doses as part of standard of care in cardiac arrest	Metoprolol 5 mg IV (up to two doses only) instead of additional epinephrine doses in cardiac arrest
Measure Participants	0	0

6. Secondary Outcome

Title	Need for Additional Antiarrhythmic Drugs
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

Data point not analyzed

Arm/Group Title	Additional Epinephrine Doses	Metoprolol
Arm/Group Description	Additional Epinephrine (1 mg) IV doses as part of standard of care in cardiac arrest	Metoprolol 5 mg IV (up to two doses only) instead of additional epinephrine doses in cardiac arrest
Measure Participants	0	0

Adverse Events

Time Frame	After Electrical Defibrillation, up to 30 days.
Arm/Group Title	Additional Doses of Epinephrine		Metoprolol Instead of Additional Doses of Epinephrine
Arm/Group Description	Epinephrine: Additional doses epinephrine (1 mg IV) as part of standard of care during cardiac arrest		Metoprolol: Metoprolol 5 mg IV (up to two times) instead of additional epinephrine doses
All Cause Mortality
	Additional Doses of Epinephrine		Metoprolol Instead of Additional Doses of Epinephrine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		5/5 (100%)
Serious Adverse Events
	Additional Doses of Epinephrine		Metoprolol Instead of Additional Doses of Epinephrine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Additional Doses of Epinephrine		Metoprolol Instead of Additional Doses of Epinephrine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/5 (0%)

Limitations/Caveats

Early termination secondary to poor enrollment

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.