Community Consultation for the Proposed Chest Pain Study

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Community Consultation for the Proposed Chest
Pain Study
DATE September 7, 2006 LOCATION Italian
Community Center Milwaukee, WI PRESENTER
Tom P. Aufderheide MD, FACEP Professor of
Emergency Medicine Froedtert Memorial Lutheran
Hospital Medical College of Wisconsin
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NIH Disclaimer

• This study is supported by the National
  Institutes of Health, National Heart, Lung and
  Blood Institute, Department of Health and Human
  Services. Its contents are solely the
  responsibility of the investigators and do not
  necessarily represent the official views of the
  National Heart, Lung and Blood Institute.

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Introductions

• Institutions Research Board (IRB)
  Representatives
• Principal Investigator
• Tom P. Aufderheide, MD, Medical College WI
• Study Funding
• National Heart, Lung and Blood Institute (NHLBI)
• Sponsor of the study
• Center for Cardiovascular Health Services
  Research at
• Tufts-New England Medical Center

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Agenda

• IMMEDIATE Trial
• Research Presentation
• Community Consultation
• Discussion

• 700 pm -- 720 pm
• 720 pm 900 pm

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Background

• In the United States each year, there are
• 1.2 million heart attacks
• 1.8 million unstable angina episodes
• 500,000 deaths 300,000 out of hospital, 200,000
  
• in hospital

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Early GIK? Dextrose in Army K Rations
(Advertisement c. 1945 LIFE Magazine) IMMEDIATE
Trial aims to translate into clinical practice
40 years of work on GIK for cardiac protection.
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Preliminary Research

• Human Studies using Glucose-Insulin-Potassium
  (GIK)
• Given too late to preserve heart muscle
• IMMEDIATE Trial
• Treatment (GIK) will be started at the earliest
  possible moment (in the ambulance)

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Why are we doing this study?

• Early recognition and treatment of heart attack
  symptoms is very important.
• To determine if an intravenous GIK solution of
  glucose, insulin, and potassium can reduce the
  likelihood of death from heart attack.
• To test whether GIK can prevent threatening heart
  attacks from occurring, and for heart attacks
  already underway, whether GIK can decrease
  serious complications and death.
• To test the use of GIK at the earliest possible
  time (in the ambulance) in the treatment of
  threatened or established heart attack This is
  the time of highest risk of death and therefore,
  greatest opportunity for saving lives.

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What is the study?

• Multi-center (nationwide)
• Wisconsin
• Massachusetts
• Texas
• Placebo-controlled (GIK or standard IV solution)
• Randomized study (50-50 chance of receiving GIK)
• Double-blind (neither patient, paramedics, or
  doctor will know which solution the patient is
  receiving)

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Randomization

• Subjects will have
• 1/2 chance of receiving standard IV of sugar
  water
• 1/2 chance of receiving GIK

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What is the study drug?

• Patients will receive either GIK or the Placebo.
• GIK
• Glucose Sugar-energy source for body-provides
  fuel to the heart when there is a reduced blood
  supply.
• Insulin Hormone, made naturally by the
  body-moves glucose into the cells.
• Potassium Salt, found in many foods and stored
  in the blood. Essential to maintain adequate
  levels.
• Placebo
• Standard IV solution of sugar and water.

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Who will be in the study?

• Potential participants must meet all of the
  following conditions
• 30 years of age or older
• Call 9-1-1 and treated by Milwaukee County
  paramedics
• Have symptoms of a heart attack such as chest
  pain or pressure, difficulty breathing, sweating
  or nausea.
• Have positive findings on an electrocardiogram
  (ECG performed by paramedics in the ambulance)
  that indicates a heart attack or lack of blood
  supply to the heart
• Paramedic believes that the patient is very
  likely to be having a heart attack or lack of
  blood supply to the heart

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Who will not be in the study?

• Less than 30 years of age
• Unconscious or unable to communicate
• Unable or unwilling to comply with study
• Undergoing dialysis for kidney disease
• Lungs congested with fluid
• Medical condition unstable, such as low blood
  pressure
• A prisoner
• Woman known to be pregnant

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What does the study involve?

• All patients who meet entry criteria and have
  symptoms of a threatened
• or established heart attack that call 9-1-1
  could be enrolled in the study.
• A 12-lead ECG or electrocardiogram will be
  acquired by paramedics to help
• determine if the patient is having a heart
  attack.
• If the patient is eligible for the study,
  paramedics will inform the patient
• about the study and ask if they want to
  participate.
• If the patient is willing to participate
• GIK or Placebo will be started by the paramedic
  in the ambulance.
• Emergency department (ED) physicians will confirm
  diagnosis.
• Out-of-hospital and in-hospital treatment is
  otherwise unchanged.
• GIK or Placebo will continue for 12 hours.

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How will a patient be enrolled?

• Paramedics will read a disclosure information
  card to the patient (and/or family member if
  available) about the study. Patients may be
  aware of the study as a result of the public
  notification process. However, there will be
  some patients who will not have heard of the
  study. This disclosure will act as reminder to
  patients who are already aware of the study and
  as information and notification of the study to
  those patients who are unaware of the study.
• Patient may tell the paramedic that he or she
  does not want to participate (decline) before the
  Study Drug is started.
• After arrival at the ED, Informed Consent will be
  obtained.
• Patient can withdraw at anytime by telling the
  medical staff. There will be no disruption in
  care.

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Study Protocol
Patient meets entry criteria
Agrees to participate
Placebo
GIK
Out-of-hospital and in-hospital treatment by
standard of care
Out-of-hospital and in-hospital treatment by
standard of care
Outcome
Outcome
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Study Protocol Continued

• Financial benefits none
• Alternative procedures none
• Confidentiality
• Information will remain confidential
• Access to medical records
• Food and Drug Administration (FDA)
• Study drug sponsor (Tufts-NEMC)
• National Institutes of Health (NIH)
• Participating Hospital Institutional Review
  Boards (IRB)
• Members of the research team

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Safety Monitoring

• Data and Safety Monitoring Board
• Monitor differences in
• Adverse events
• Survival rates

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Differences Between Treatment and Research

• Treatment
• Proven to be effective
• Established as acceptable practice
• Involves risks and benefits
• Research
• Attempts to advance knowledge and improve
  treatment
• Unproven (experimental) intervention
• Randomize
• Involves risks and benefits

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What are the potential benefits of GIK?

• Might increase the likelihood of survival
• May decrease or slow the damage to the heart
• May allow other treatments to have a better
• chance of working
• May reduce the likelihood of congestive heart
• failure following a heart attack

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What are the risks?

• Death from a heart attack or lack of blood supply
  to the heart is a risk
• regardless of participation in the study
• Unknown or unanticipated risk
• Redness, soreness or inflammation at the IV site.
• Change in potassium level (high or low) which may
  cause palpitations
• (heart is beating fast) or dizziness.
• Change in blood sugar levels (high or low) that
  could cause weakness,
• dizziness or thirstiness.
• Increased fluid in lungs. from 12 hours of IV
  solution. In very few
• people, (Less than 1 out of 1,000 subjects
  with a heart attack treated
• with GIK) medication is necessary to get rid
  of extra fluid.
• Loss of confidentiality related to medical
  records review.

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Study Duration Timeline Plans for Enrollment

• Study Start Summer 2006
• Study Duration 28 months
• 24 hours a day / 7 days a week
• 60,000 patients will be screened nationwide,
  12,000 locally
• 15,450 patients will be enrolled nationwide,
  3,000 locally

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Study Approval

• Study will not proceed without final approval
  from
• Local Institutions Research Boards (IRB)
• Investigational New Drug (IND) exemption from the
  Food and Drug Administration

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Why are we all here?

• Enrollment in the IMMEDIATE Trial is being
  performed under
• emergency circumstances.
• Patients may not be physically or emotionally
  able to
• understand the study and make an informed
  decision to
• participate. In order for GIK to have the
  highest likelihood
• to benefit the patient, it must be initiated
  as soon as possible
• after the onset of symptoms.
• Therefore the FDA has required that the process
  of exception
• to informed consent under emergency
  circumstances be
• implemented for the out-of-hospital or
  paramedic phase of
• the study.

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Exception from Informed Consent Requirements for
Emergency Research

• Informed Consent
• Exception issued by Food and Drug Administration
  (FDA)
• Exception to informed consent under emergency
  circumstances

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Food and Drug Administration (FDA) Requirements
for Exception to Informed Consent
A. IRB with concurring physician finds and
documents 1. Life threatening situation with
unproven or unsatisfactory treatment and
research is necessary 2. Obtaining informed
consent is not feasible 3. Participation in
research has prospect of direct benefit
because i. Situation necessitates
intervention ii. Science supports potential of
direct benefit iii. Risks are reasonable compared
to medical condition 4. Research could not
practicably be done without waiver 5. Potential
therapeutic window is short 6. IRB approves
consent document and procedures for subject or
legal representative
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Food and Drug Administration (FDA) Requirements
for Exception to Informed Consent (Continued)
B. Information provided to subject, legal
representative, and/or family as soon as
possible C. Documentation will be kept on file in
accordance with IRB regulations D. Separate
investigational new drug (IND) exemption
obtained from FDA E. Additional protections i.
Public disclosure prior to initiation ii. Public
disclosure after completion iii. Independent Data
and Safety Monitoring Board iv. Attempt to
contact family member when possible v. Community
consultation
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For more information please contact Tom P.
Aufderheide MD, FACEP Department of Emergency
Medicine 9200 West Wisconsin Avenue, Froedtert
East Milwaukee, Wisconsin 53226 Office (414)
805-2572 Fax [phone] Email
taufderh_at_mcw.edu www.IMMEDIATETrial.com