|NHLBI Stops Enrollment in Study on Resuscitation
Methods for Cardiac Arrest
Different CPR Durations Found Equally Successful; CPR Device
Does Not Add Benefit
Enrollment has ended early in a large, multicenter clinical trial
comparing two distinct resuscitation strategies delivered by emergency
medical service (EMS) providers to increase blood flow during cardiac
arrest. The study's independent monitoring board and the National
Heart, Lung, and Blood Institute (NHLBI), the lead sponsor of the
study, stopped enrollment based on preliminary data suggesting
that neither strategy significantly improved survival. One strategy
compared different durations of manual cardiopulmonary resuscitation
(CPR) by EMS providers before they assessed whether defibrillation
was needed, and the other strategy tested the potential benefits
and risks of an investigational device to maintain pressure in
the chest during CPR.
After reviewing data on approximately 11,500 study participants,
the study's Data and Safety Monitoring Board (DSMB) recommended
on Oct. 23 that the NHLBI stop enrollment because sufficient data
had been gathered, and continuing recruitment was unlikely to change
the overall outcomes of the study. The board had no concerns about
the safety of any of the interventions tested, and NHLBI accepted
the DSMB recommendations on the same day. Researchers will continue
to monitor study participants who agree to follow-up visits for
up to six months. They will analyze and publish the final data
in the coming months. The NHLBI is part of the National Institutes
"Survival rates for patients who suffer cardiac arrest before
reaching a medical facility are tragically low," said Susan
Shurin, M.D., deputy director of the NHLBI, who oversees clinical
trials supported by NHLBI and accepted the DSMB recommendation." This
study provides important evidence to help inform first responders
and other health care providers on safe and effective life-saving
treatment options. We will continue to search for new ways to save
lives in the precious few moments after cardiac arrest – and evaluate
the benefits and risks of commonly used practices."
The Resuscitation Outcomes Consortium (ROC), the largest clinical
research network to study prehospital treatments for cardiac arrest
in the United States and Canada, tested both resuscitation strategies
as part of the Prehospital Resuscitation using an IMpedance valve
and Early versus Delayed (ROC PRIMED) clinical trial. An impedance
valve, also called an impedance threshold device (ITD), is a small,
hard plastic device about the size of a fist that is attached to
the face mask or breathing tube during CPR administered by EMS
providers. The device is designed to improve circulation by enhancing
changes in pressures within the chest during CPR. Researchers found
that ITD use did not significantly improve or worsen survival rates
for cardiac arrest patients.
The early versus delayed strategy compared two currently used
timing strategies of assessing the heart's rhythm in relation to
when CPR is started by EMS providers. The heart rhythm assessment
is done to determine whether defibrillation to restore the heart
to its normal rhythm is needed. The study compared patient survival
rates after EMS providers performed at least 30 seconds of CPR
before assessing the need for defibrillation with delivering three
minutes of CPR before the assessment. Based on current study data,
both timing strategies were equally effective.
EMS providers assess approximately 350,000 people with cardiac
arrest in the United States each year. Only 5 to 10 percent of
people who have sudden cardiac arrest survive. When administered
as soon as possible, CPR and, in some cases, rapid treatment with
a defibrillator — a device that sends an electric shock to
the heart to try to restore its normal rhythm — can be lifesaving.
When delivered by EMS professionals, CPR is a combination of chest
compressions, to keep oxygen-rich blood circulating until an effective
heartbeat is restored, and rescue breathing. Lay bystanders are
encouraged to immediately begin CPR using only chest compressions
until professional help arrives, according to the American Heart
ROC PRIMED was designed to test the two promising strategies to
increase the chance of survival without functional impairments
of patients who suffer cardiac arrest outside of a hospital setting.
To test the ITD strategy, patients were randomly assigned to receive
standard CPR from participating EMS providers either with an ITD
or with a non-working replica (sham) of an ITD.
In animal studies and in small studies in humans, the ITD has
been shown to markedly increase blood flow to the heart and to
raise blood pressure. Human studies have also showed a tendency
toward improved short-term outcomes without adverse effects. A
modified version of the ITD is approved by the Food and Drug Administration
(FDA) for use in conditions other than cardiac arrest.
However, a large human clinical trial was needed to show whether
the device significantly improves survival with preserved neurologic
function. Patients with preserved neurologic function are able
to carry out activities of daily living. In contrast, patients
who suffer neurological damage following cardiac arrest may no
longer be able to care for themselves due to injury to parts of
The study's preliminary results indicate similar survival rates
of patients with preserved neurologic function between both groups
of patients, suggesting that standard CPR without an ITD is as
effective as using an ITD.
"While the ITD is based on a sound physiologic principle,
in this study it did not appear to improve survival rates for adults
in cardiac arrest outside of the hospital," said Tom Aufderheide,
M.D., a professor of emergency medicine at the Medical College
of Wisconsin in Milwaukee and a ROC principal investigator. "We
will continue to seek out and thoroughly test new devices as well
as alternative applications that hold promise for saving the lives
of cardiac arrest patients."
The other principal strategy studied in ROC PRIMED was the timing
of assessing the heart's rhythm to determine whether defibrillation
is needed in relation to when CPR is started. For patients randomly
assigned to the Analyze Early group, EMS providers were instructed
to perform CPR until they were able to analyze the patient's heart
rhythm (approximately 30 to 90 seconds). Patients in the Analyze
Later group received CPR for at least three minutes before their
heart rhythm was analyzed. When indicated, defibrillation was provided.
Some smaller studies have suggested that longer periods of CPR
before defibrillation might increase survival, while other studies
have suggested that more immediate defibrillation — when
the patient is treated within two minutes after the start of cardiac
arrest — might be better.
"The ROC PRIMED study answers a long-standing question in
the EMS community over whether it is better to defibrillate earlier
or later when trying to resuscitate a patient," said Ian Stiell,
M.D., professor and chair of the Department of Emergency Medicine
at the University of Ottawa, senior scientist at the Ottawa Hospital
Research Institute, and a principal investigator for the ROC PRIMED
Analyze Early vs. Later protocol. "Both techniques appear
to be equally beneficial."
Myron Weisfeldt, M.D., ROC Steering Committee chair and director
of the Department of Medicine at the Johns Hopkins University School
of Medicine in Baltimore, added, "Questions like this one — which
address the relative benefits of current medical practices — are
an important example of comparative effectiveness research and,
in this case, can help advance emergency medical care."
ROC PRIMED and other ROC clinical trials are conducted under strict
U.S. FDA and Canadian guidelines that allow for patients in life-threatening
situations to participate in research under an exception to explicit
informed consent, according to U.S. and Canadian laws. This is
necessary because, among other reasons, participants in cardiac
arrest are unconscious and therefore cannot give consent. Before
any patients were enrolled, communities were consulted about participation
and made aware that informed consent will not be obtained for most
study participants, as required by law.
To ensure patient safety during the study, the DSMB that monitors
ROC studies reviews the accrued data approximately every six months
or more frequently if needed. The ROC DSMB includes experts in
trauma, cardiac arrest, statistics, ethics, and the conduct of
clinical trials. During its interim data review on Oct. 23, the
DSMB recommended stopping enrollment in both ROC PRIMED assessments
based on results that suggest that both types of strategies were
equally beneficial and that continued enrollment was unlikely to
yield different results. The NHLBI accepted the recommendation,
and ROC clinical sites stopped enrollment.
The ROC is a large clinical research network of 10 centers in
the United States and Canada. Approximately 150 EMS and fire services
organizations, involving more than 20,000 EMS providers who serve
a combined population of nearly 15 million people from diverse
urban, suburban, and rural regions participated in ROC PRIMED.
ROC research focuses on treatments for patients with life-threatening
traumatic injury or cardiac arrest in real-world settings, typically
where patients collapse or are critically injured, before they
reach the hospital. Participating EMS providers receive intensive
training, and give standard emergency care to all patients, with
some patients randomly selected to receive the intervention to
be tested in addition to usual care.
"The ROC is the largest research network to study real-world,
pre-hospital interventions for cardiac arrest," noted George
Sopko, M.D., ROC project officer in the NHLBI Division of Cardiovascular
Sciences. "Conducting these studies through this robust and
experienced network allows us to implement and compare clinical
interventions in meaningful ways and to disseminate the results
as quickly as possible so they can be applied to improve public
Earlier this year, the NHLBI stopped enrollment early for two
ROC clinical trials that examined whether concentrated (hypertonic)
saline improved survival over standard saline for trauma patients.
Patients in the study were either suffering from shock due to significant
blood loss or had experienced a traumatic brain injury. In both
types of patients, hypertonic saline solution did not improve outcomes
over the use of a standard saline solution.
The NHLBI is the lead federal sponsor of the ROC studies. Additional
funding is provided by the NIH's National Institute of Neurological
Disorders and Stroke, the Institute of Circulatory and Respiratory
Health of the Canadian Institutes of Health Research, US Army Medical
Research & Materiel Command, American Heart Association, Defence
Research and Development Canada, and the Heart and Stroke Foundation
Further information about this trial (NCT00394706) can be found
To interview an NHLBI spokesperson, contact the NHLBI Communications
Office at 301-496-4236 or at nhlbi
firstname.lastname@example.org. To interview Dr. Aufderheide, contact Toranj
Marphetia at 414-456-4744 or email@example.com.
To interview Dr. Stiell, contact Jennifer Paterson at 613-798-5555
x 73325 or firstname.lastname@example.org.
To interview Myron Weisfeldt, M.D., ROC Steering Committee chair,
contact David March at 410-955-1534 or email@example.com.
Part of the National Institutes of Health, the National Heart,
Lung, and Blood Institute (NHLBI) plans, conducts, and supports
research related to the causes, prevention, diagnosis, and treatment
of heart, blood vessel, lung, and blood diseases; and sleep disorders.
The Institute also administers national health education campaigns
on women and heart disease, healthy weight for children, and other
topics. NHLBI press releases and other materials are available
online at: www.nhlbi.nih.gov.
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Medical Research Agency — includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services.
It is the primary federal agency for conducting and supporting basic,
clinical and translational medical research, and it investigates
the causes, treatments, and cures for both common and rare diseases.
For more information about NIH and its programs, visit www.nih.gov.