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IMMEDIATE-2 Trial Frequently Asked Questions
1. What is the IMMEDIATE-2 Trial?
The IMMEDIATE-2 Trial is a study to evaluate if an investigational IV solution of glucose, insulin and potassium (GIK) is helpful to patients with signs and symptoms of Acute Coronary Syndrome (ACS). GIK is believed to provide metabolic support to the myocardium and can potentially extend the time window for benefit from coronary reperfusion therapies, and other supportive care. The IMMEDIATE-2 Trial follows on from the IMMEDIATE Trial, which was funded by the National Heart, Lung and Blood Institute (NHLBI) from 20006-2011 with the same objective.
2. What were the results of the IMMEDIATE Trial?
The IMMEDIATE Trial did not meet its primary endpoint (progression to myocardial infarction). However it did significantly reduce the composite endpoint of cardiac arrest or mortality - by 50% for those presenting with suspected ACS, and by 60% for those presenting with ST elevation AMI (STEMI). Also, GIK reduced infarct size by 80%.
3. How is IMMEDIATE-2 different from the original IMMEDIATE Trial?
The primary endpoint for the IMMEDIATE Trial was progression to myocardial infarction. The primary endpoint for the IMMEDIATE-2 Trial is the Finkelstein-Schoenfeld hierarchical combination endpoint of 30-day all-cause mortality, in-hospital cardiac arrest, or infarct size measured 30 days from the index hospitalization. The original IMMEDIATE Trial enrolled participants only in the Emergency Medical Services (EMS) while the IMMEDIATE-2 Trial will enroll in both EMS and in emergency departments (EDs), to address the fact that half of all patients with ACS do not come to hospitals via EMS, but present directly to the ED.
4. How many participants will be enrolled in the IMMEDIATE-2 Trial?
1,600 participants with symptoms consistent with ACS will be identified by EMS paramedics in the field prior to transport to the receiving hospital, or identified by ED staff upon direct presentation to the hospital. All 1,600 participants will be randomized to receive a 12-hour IV infusion of either GIK or placebo. Data on this cohort will be collected for two years following treatment. The first 900 consenting participants also will be enrolled in an FDA Accelerated Approval Path Cohort.
5. How many sites will participate in IMMEDIATE-2?
Approximately 25 sites across the US will participate in IMMEDIATE-2 and will be a mix of large academic medical centers and smaller community hospitals.
6. Where will enrollment take place?
Enrollment for IMMEDIATE-2 will take place in the EMS system by paramedics following a 911 call, and in the ED, to include those patients who go directly to the ED.
7. What is in the GIK solution?
The GIK solution will be the same as that used in the IMMEDIATE Trial, consisting of 30% dextrose in water, 50 units of regular insulin per liter, and 80 mEq of KCl per liter, given intravenously at 1.5 ml/kg/hour. The placebo control is 5% dextrose per liter.
8. How safe is GIK?
GIK has a very favorable safety profile. There have been a number of clinical and laboratory studies conducted on GIK in the past 60 years that have shown. Over 12,000 participants in international multi-center randomized control trials have received GIK infusions with minimal adverse events reported, and no serious adverse events.
9. Who is eligible for enrollment?
People are eligible for enrollment if they meet the following criteria

1. Age ? 30 years

2. Symptoms of ACS including, but not limited to:
  • Chest pain / discomfort / tightness
  • Arm, shoulder pain
  • Jaw pain
  • Epigastric discomfort
  • Shortness of breath

    3. 12-lead ECG with at least one of the following:
  • ACI-TIPI score of 75% or more
  • Thrombolytic Predictive Instrument activated
  • ECG shows a definitive acute MI with ST segment elevation based on local criteria
  • 10. Is there a time threshold for treatment with GIK?
    Patients who call 911 will be seen by an EMS paramedic in a matter of minutes, and randomized to the study drug at that time. Patients who present directly to the ED must be treated within three hours of symptom onset.
    11. What is the Informed Consent process?
    Given the safety of the intervention and the need to not disrupt EMS or ED patient care, we will use the Exception from Informed Consent (EFIC) Requirements for Emergency Research. EFIC was used in the original IMMEDIATE Trial following consultation with experts at FDA and the Office of Human Research Protection (OHRP), and participating IRBs. As in the original IMMEDIATE Trial we will augment this by also getting informed consent in the hospital, when the participant is medically stable. The EFIC procedure includes:
  • Information card read to patient by paramedic to get assent prior to randomization
  • Written consent will be requested when the participant is stable at receiving hospital
  • 12. Is there a time frame for obtaining informed consent?
    Full written consent should be requested and obtained as soon as feasible after patient has been stabilized in the hospital.
    13. How long will the participant be in the study?
    The participant will receive the study drug IV infusion for 12 hours. The participant will receive follow-up phone calls from the ED Study Coordinator/Nurse at 30 days, one year and two years.
    14. What is the ACI-TIPI tool?
    The IMMEDIATE-2 Trial uses an ACI TIPI Score of >75% probability of Acute Cardiac Ischemia (ACI) as one of the eligibility criteria. The ACI-TIPI (Acute Cardiac Ischemia Time-Insensitive Predictive Instrument) is a software tool that enhances the decision making process for EMS paramedics and ED staff and physicians when reviewing 12lead ECG results. ACI-TIPI is built into the electrocardiograph or defibrillator and generates a predicted probability score of ACI based on both ECG features, and patient demographic information such as age, gender, and chest pain status. The probability score supports EMS and ED personnel's efforts to decrease time from the onset of ACI symptoms to treatment with interventional cardiology.
    15. When would GIK be given - immediately during CPR or after CPR/ROSC?
    This Trial will enroll patients who present with chest pain or other symptoms of ACS, not those who present with cardiac arrest and require CPR, and those with Killip 3 or 4 AMIs are excluded, due to the potential deleterious effect of fluid load. As per the original IMMEDIATE Trial, in IMMEDIATE-2, GIK will be administered as soon as possible following presentation (in EMS or ED settings) without interrupting patient care. GIK must be administered before the patient goes to the cath lab.
    16. Will the screening/enrollment process affect patient care?
    Participation in the IMEMDISATE-2 Trial will not result in any treatment delays. The entire screening/enrollment/consent process added an average of one minute to the entire pre-treatment process in the first IMMEDIATE Trial. All standard of care procedures and treatments should continue during the infusion, including emergency procedures such as cardiac catheterization.
    17. What is required of the EMS Paramedic?
    The paramedic is responsible for the following:
  • Screening all patients who call 911 and are experiencing symptoms suggestive of ACS for IMMEDIATE-2 Trial eligibility.
  • The screening process involves a clinical assessment by the Paramedic as well as review of a 12-Lead ECG. If a 12-lead ECG is done then a Screening Form for enrollment must be completed.
  • If the patients meets the eligibility criteria, reading the Trial Information Card to the patient, asking if they would like to participate in the study
  • If assent is provided, randomizing the patient to Study Drug
  • Ensuring hand-off of Study Drug Packet and documentation to appropriate ED personnel (Study Coordinator or Nurse)
  • Ensure all required study documentation is completed
  • 18. What is required of ED Study Coordinator/Nurse? For patients presenting directly to the ED, the Study Coordinator/Nurse is responsible for the following:
    1. Conducting the screening process and ensure an ECG is performed.
    2. Following the initial assessment, if the participant is eligible for the study, the Study Coordinator/Nurse will read the Trial Information Card to the patient and, if they assent, will administer an IV of either GIK or placebo.
    3. Request written Informed Consent as soon as is feasible once the participant is finalized
    4. Ensuring blood work is drawn for baseline glucose and potassium levels, and again at 6 and 12 hours.
    5. Ensure that the Study Drug Packet moves with the participant if they are being transferred to the cath lab.
    6. Complete all study documentation and enter all required data into the electronic Case Report Form
    7. Monitor the participant over the 12 hour Study Drug infusion
    8. Schedule the participant's sestamibi scan to assess infarct size
    9. Conduct follow-up phone calls at 30 days, six months, one-year and two-years to assess mortality, hospitalization and patient-reported outcomes of participant
    19. For participants coming to a receiving hospital from EMS, the following steps are taken.
    The Paramedic will have screened and randomized the participant to Study Drug. The Paramedic will inform the ED Study Coordinator/Nurse that a subject has been enrolled in the study and will assist them in the transfer of the pre-hospital IV to the ED IV. The Study Procedures will continue with Steps 4-9 as outlined above.
    20. What is required of ED physicians?
    The ED physician assesses the participant. If they determine that the patient does not have ACS, the physician will stop the study drug infusion.

    If a diagnosis of ACS is confirmed, he/she will write the following orders
  • The patient is enrolled in the IMMEDIATE-2 Trial
  • Continue the study drug infusion
  • Monitor fluid status and blood glucose and potassium at baseline, 6 and 12 hours. If the physician becomes concerned about the participants health or safety, they may stop the infusion at any time.
  • 21. Will all study staff receive training?
    Yes. Prior to the start of the IMMEDIATE-2 Trial all EMS and ED personnel at participating sites must complete the Trial's training requirements which include an online course, and a hands on practicum session. It is estimated that training will take approximately eight hours to complete, and can be completed over a number of sessions at the convenience of the staff member. Paramedic training time will be covered at time and a half and all study staff will receive continuing education credits.