Clinical trial NCT00781118: AngelMed for Early Recognition and Treatment of STEMI
Official title: AngelMed for Early Recognition and Treatment of STEMI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myocardial Infarction (AMI)
Coronary Occlusion
Acute Coronary Syndrome
Keywords: Acute Myocardial Infarction (MI)
ST Shift
Coronary Occlusion
Acute Coronary Syndrome
Lead sponsor: Angel Medical Systems
Sponsor class: INDUSTRY
Collaborators: name: Symbios Clinical
First posted: 2008-10-28
Enrollment: 1020
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: A prospective, randomized multicenter study of subjects with a high-risk of having a myocardial infarction (MI) due to acute coronary syndrome or bypass surgery. There is no differential intervention administered to the two arms of the ALERTS Study. The study evaluates whether or not a patient alarm from the Guardian System will provide benefit (e.g. shorten pre-hospital delay) compared to symptoms-only ER presentation in the event of a heart attack. An amendment to the data analysis protocol was collaboratively created by AngelMed and FDA, and was adopted by AngelMed on 4/22/2017.

Detailed description: There are over one million acute myocardial infarctions (AMI) each year in the United States with more than 400,000 of these resulting in death. Early identification of AMI, and prompt treatment has been shown to significantly improve clinical outcomes. Experimental and clinical studies have shown that most of the irreversible damage to the myocardium occurs during the first two hours after coronary occlusion. Milavetz et al. demonstrated that successful reperfusion therapy within two hours was associated with the greatest degree of myocardial salvage. According to Boersma, et al., restoration of flow, regardless of the method used, can abort infarction within the first 30 minutes after coronary occlusion, and the benefit of fibrinolytic therapy compared with placebo is considerably higher in patients treated within 2 hours after symptom onset than in those treated later.2 Further, evidence exists that expeditious restoration of flow in the obstructed infarct artery after the onset of symptoms in patients with the most severe type of MI, ST elevation MI (STEMI) is a key determinant of short and long-term outcomes regardless of whether reperfusion is accomplished by fibrinolysis or percutaneous coronary intervention (PCI). Therefore, the early arrival at the hospital for a reliable diagnosis and initiation of treatment is paramount to improve the outcomes of myocardial infarction. However, despite efforts at educating the public over the past decade, the mean time from AMI symptom onset to arrival at a hospital for treatment has remained, disappointingly, at 2.5-3.0 hours.

The largest proportion of the total pre-hospital delay is the interval between the onset of symptoms and the decision to seek medical treatment. Finnegan et al. described that the reasons for delay in seeking medical evaluation generally stem from patient misconceptions about symptom experience, expectations, and attribution. In many cases, patients expect the type of heart attack that they often see in movies or on television: the kind of crushing chest pain that drops a person to the ground. The reality is that many heart attacks are much "quieter," causing only mild chest pain or discomfort or other symptoms such as shortness of breath or diaphoresis.

If patients would take action during the first hour following symptom onset, many lives and significant cost could be saved. It is technically possible to monitor EKGs and detect an acute infarction, even if the patient is unaware that he or she is experiencing a heart attack. However, currently available systems have limitations in the home environment. Twelve lead EKG systems require a clinically trained individual to place them. Holter monitors suffer from limitations in the ability to detect ST deviation due to low compliance and are limited in practice to 24 to 72 hours of monitoring. Systems using surface leads are all subject to noise and other artifacts from patient movement and body orientation, particularly if the patient is ambulatory.

A potentially ideal solution is to implant a device that measures heart signals from inside the heart and will alert the patient when it detects electrogram characteristics set by the physician as worthy of medical evaluation.

Eligibility criteria: Inclusion Criteria:

* Subject has at least one of the following conditions:

  1. Diabetes (Type I or Type II)
  2. Compromised renal function (Cr \> 1.2 mg/dl or creatinine clearance less than 50)
  3. TIMI Risk Score ≥ 3
* Presents (within past 6 months) with a high-risk acute coronary syndrome (e.g., Unstable Angina, STEMI or NSTEMI) or has undergone or is scheduled for CABG within 6 months of implantation.
* Has already undergone coronary angiography and revascularization, unless the physician determines it is appropriate to implant before or during the planned procedure.
* Lives in a geographic area in close proximity (within 60 minutes by EMS) to any hospital that can treat AMI.
* Subjects (men or women) at least 21 years of age. Women of childbearing age must have a negative pregnancy test or confirmation of one of the following:

  1. Post-menopause or amenorrheic during the past year
  2. Surgical sterilization
  3. Use of effective contraceptive method

Exclusion Criteria:

* In the investigator's opinion, subject lacks ability to respond appropriately to alarms, e.g., illiteracy, poor memory or cognitive function, dementia or other condition affecting memory function, etc.
* There is known compromised tissue at the site of lead implantation in the apex of the right ventricle, e.g., prior infarct affecting the RV apex location.
* A permanent pacemaker or ICD is already in place or the patient is indicated for ICD or pacemaker implantation based on the guidelines published by the American College of Cardiology as Class I and IIa recommendations. Class IIb recommendations are at the investigator's discretion.
* Subject cannot feel the IMD vibration when placed on top of the skin on the left pectoral side of the chest.
* Subject has recurrent or persistent atrial fibrillation.
* Subject has recurrent or persistent non-sinus cardiac rhythm, second or third degree atrioventricular blocks, QRS duration greater than 120 ms, Benign Early Repolarization (BER), or Brugada Syndrome.
* Subject has left ventricular hypertrophy evidenced by EKG criteria.
* Subject has any condition preventing the subcutaneous implantation of the Guardian System in a left pectoral pouch, such as: superior vena cava thrombosis, subcutaneous tissue deemed inappropriate for the procedure or prior central venous access via portacath, Hickman, Groshong, or similar placed in a left pectoral location or left side PICC line.
* Subject has extremely heavy alcohol consumption (participates in binge drinking that leads to alcohol intoxication) or has history of alcohol or illicit drug abuse within past 5 years.
* There is evidence of unresolved infection (fever \> 38° C and/or leukocytosis \> 15,000).
* Subject has history of bleeding disorders or severe coagulopathy (platelets \< 100,000 plts/ml; APTT or PT \> 1.3 x reference range).
* Subject has had a hemorrhagic stroke or transient ischemic attack (TIA) in the past 6 months.
* Subject has other severe diseases, such as cancer or refractory congestive heart failure, associated with limitation of life expectancy (less than 1 year), which may lead to inadequate compliance to the protocol or confusing data interpretation.
* Subject has clinical conditions such as heart diseases, difficult-to-control blood pressure, difficult-to-control insulin-dependent diabetes or serious prior infections attributed to the diabetes, or others that, at the investigator's discretion, could seriously affect the subject's current clinical condition during study procedures.
* Subject has previous participation in the DETECT Study, current participation or previous participation in another drug or device study in the past 30 days that conflicts with this study as determined by the study sponsor.
* Subject has experienced gastro-intestinal hemorrhage in the past 6 months.
* Subject has any situation in which the use of aspirin is contraindicated for at least 6 months.
* Subject has epilepsy.
* Subject has known severe allergies, e.g., peanut, bee sting, etc.

Primary outcomes:
measure: The primary efficacy objective is to determine that the Guardian System reduces the composite of Cardiac or unexplained death, new Q-wave MI and time to door for a confirmed occlusive event at a medical facility >2 hours.
timeFrame: Due to Bayesian statistical analysis, the study data will be analyzed after subject enrollment reaches 600, 900, 1200, etc. With amendment the study period spanned from December 2008 until database lock April 1, 2014.
Secondary outcomes:
measure: - Reduction of the incidence of cardiac death or unexplained death during follow-up - Reduction of the incidence of "New" Q-wave myocardial infarction in one or more distributions during follow-up- Reduction of the time to door for confirmed STEMI.
timeFrame: Due to Bayesian statistical analysis, the study data will be analyzed after subject enrollment reaches 600, 900, 1200, etc With amendment the study period spanned from December 2008 until database lock April 1, 2014.
measure: Secondary Endpoint #2
timeFrame: With amendment the study period spanned from December 2008 until database lock April 1, 2014.
measure: Secondary Endpoint #3
timeFrame: With amendment the study period spanned from December 2008 until database lock April 1, 2014.
measure: Secondary Endpoint #4
timeFrame: With amendment the study period spanned from December 2008 until database lock April 1, 2014.
measure: Secondary Endpoint #5
timeFrame: With amendment the study period spanned from December 2008 until database lock April 1, 2014.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology, P.C.
state: Alabama
city: Huntsville
country: United States
facility: Heart Center Research/Huntsville Hospital
state: Alabama
city: Mesa
country: United States
facility: Banner Heart Hospital
state: Arizona
city: Phoenix
country: United States
facility: Banner Good Samaritan Medical Center
state: Arizona
city: Tucson
country: United States
facility: Southwest Heart Group
state: Arizona
city: Concord
country: United States
facility: John Muir Clinical Research Center
state: California
city: Glendale
country: United States
facility: California Clinical Research Foundation
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Mission Viejo
country: United States
facility: Mission Internal Medical Group
state: California
city: Orange
country: United States
facility: Orange County Heart Institute and Research Center Hospital
state: California
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Sacramento
country: United States
facility: Sutter Memorial Hospital
state: California
city: Salinas
country: United States
facility: Salinas Valley Memorial Hospital
state: California
city: Santa Rosa
country: United States
facility: Radiant Research
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Bay Pines
country: United States
facility: Bay Pines VA Healthcare System
state: Florida
city: Daytona Beach
country: United States
facility: Daytona Heart Group
state: Florida
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Gainesville
country: United States
facility: NorthFL/South GA VA Health System
state: Florida
city: Miami Beach
country: United States
facility: New Phase Clinical Trials
state: Florida
city: Miami
country: United States
facility: Mercy Research Institute
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: New Smyrna Beach
country: United States
facility: Complete Cardiology Care
state: Florida
city: Saint Augustine
country: United States
facility: East Coast Institute for Research
state: Florida
city: Tampa
country: United States
facility: Univeristy of South Florida
state: Florida
city: Tampa
country: United States
facility: Florida Hospital - Pepin Heart Institute
state: Florida
city: Macon
country: United States
facility: The Medical Center of Central Georgia
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Medical Group
state: Illinois
city: Bloomington
country: United States
facility: Premier Healthcare
state: Indiana
city: Fort Wayne
country: United States
facility: Northern Indiana Research Alliance
state: Indiana
city: Merrillville
country: United States
facility: Heart Center of Lake County
state: Indiana
city: Muncie
country: United States
facility: Medical Consultants, PC
state: Indiana
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Covington
country: United States
facility: Innovative Medical Research
state: Louisiana
city: Hammond
country: United States
facility: Heart Clinic of Hammond
state: Louisiana
city: Slidell
country: United States
facility: Louisiana Heart Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Bethesda
country: United States
facility: Suburban Hospital - Johns Hopkins Medicine
state: Maryland
city: Pikesville
country: United States
facility: Woodholme Cardiovacular Associates
state: Maryland
city: Takoma Park
country: United States
facility: Washington Adventist Hospital
state: Maryland
city: Bay City
country: United States
facility: McLaren Bay Region
state: Michigan
city: Detroit
country: United States
facility: DMC Cardiovascular Institute at Harper-Hutzel Hospital
state: Michigan
city: Farmington Hills
country: United States
facility: Detroit Clinical Research Center
state: Michigan
city: Flint
country: United States
facility: Cardiology Consultants of East Michigan
state: Michigan
city: Grand Blanc
country: United States
facility: Genesys Regional Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Mount Clemens
country: United States
facility: McLaren Macomb
state: Michigan
city: Petoskey
country: United States
facility: Cardiac & Vascular Research Center of Northern Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: University of Medicine & Dentistry NJ
state: New Jersey
city: Newark
country: United States
facility: St. Michael's Medical Center
state: New Jersey
city: Voorhees
country: United States
facility: Lourdes Cardiology Services
state: New Jersey
city: Albany
country: United States
facility: Albany Associates in Cardiology
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Buffalo
country: United States
facility: Buffalo Heart Group - Mercy Hospital of Buffalo
state: New York
city: Buffalo
country: United States
facility: Buffalo Heart Group - Millard Fillmore Gates Circle Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Williamsville
country: United States
facility: Cardiology Group of Western New York
state: New York
city: Raleigh
country: United States
facility: REX Healthcare
state: North Carolina
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Toledo
country: United States
facility: Cardiovascular Research Center
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Oklahoma City
country: United States
facility: South Oklahoma Heart Research
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Langhorne
country: United States
facility: St. Mary Medical Center Research Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny-Singer Research Institute
state: Pennsylvania
city: Sayre
country: United States
facility: Donald Guthrie Foundation for Education & Research
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley Heart Hospital
state: Pennsylvania
city: York
country: United States
facility: Cardiac Diagnostic Associates/York Hospital
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System
state: South Carolina
city: Germantown
country: United States
facility: Stern Cardiovascular Center
state: Tennessee
city: Knoxville
country: United States
facility: Turkey Creek Medical Center
state: Tennessee
city: Nashville
country: United States
facility: St. Thomas Research Institute
state: Tennessee
city: Amarillo
country: United States
facility: Cardiology Center of Amarillo
state: Texas
city: Houston
country: United States
facility: West Houston Area Clinical Trial Consultants
state: Texas
city: Houston
country: United States
facility: West Houston Area Clinical Trial Consultants
state: Texas
city: Temple
country: United States
facility: Scott and White Healthcare
state: Texas
city: Tyler
country: United States
facility: Tyler Cardiovascular Consultants
state: Texas
city: Fredericksburg
country: United States
facility: Cardiology Associates of Fredericksburg
state: Virginia
city: Manassas
country: United States
facility: Virginia Cardiovascular Associates
state: Virginia
city: Newport News
country: United States
facility: Riverside Regional Medical Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Institute
state: Virginia
city: Virginia Beach
country: United States
facility: Cardiovascular Associates, Ltd
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center/Cardiovascular Research
state: Washington
Study officials:
References:
citation: Holmes DR Jr, Krucoff MW, Mullin C, Mikdadi G, Presser D, Wohns D, Kaplan A, Ciuffo A, Eberly AL 3rd, Iteld B, Fischell DR, Fischell T, Keenan D, John MS, Gibson CM. Implanted Monitor Alerting to Reduce Treatment Delay in Patients With Acute Coronary Syndrome Events. J Am Coll Cardiol. 2019 Oct 22;74(16):2047-2055. doi: 10.1016/j.jacc.2019.07.084.
citation: Gibson CM, Holmes D, Mikdadi G, Presser D, Wohns D, Yee MK, Kaplan A, Ciuffo A, Eberly AL 3rd, Iteld B, Krucoff MW. Implantable Cardiac Alert System for Early Recognition of ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol. 2019 Apr 23;73(15):1919-1927. doi: 10.1016/j.jacc.2019.01.014. Epub 2019 Mar 3.
citation: Rogers T, Steinvil A, Torguson R, Waksman R. Overview of the 2016 US Food and Drug Administration Circulatory System Devices Panel Meeting on the AngelMed Guardian System. Circulation. 2016 Jul 19;134(3):262-4. doi: 10.1161/CIRCULATIONAHA.116.023081. No abstract available.
citation: Gibson MC, Krucoff M, Fischell D, Fischell TA, Keenan D, Abueg C, Patel C, Holmes D. Rationale and design of the AngeLmed for Early Recognition and Treatment of STEMI trial: a randomized, prospective clinical investigation. Am Heart J. 2014 Aug;168(2):168-74. doi: 10.1016/j.ahj.2014.05.008. Epub 2014 May 24.