AngelMed for Early Recognition and Treatment of STEMI

Acute Coronary Syndrome Clinical Trial

— ALERTS  

Official title:

AngelMed for Early Recognition and Treatment of STEMI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00781118
• Other study ID #: ALERTS Study
• Status: Completed
• Phase: Phase 3
• First received: October 24, 2008
• Last updated: March 9, 2018
• Start date: December 2008
• Est. completion date: May 17, 2017

Study information

• Verified date: March 2018
• Source: Angel Medical Systems
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1020
• Est. completion date: May 17, 2017
• Est. primary completion date: May 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Myocardial Infarction (AMI)
• Coronary Occlusion
• Infarction
• Myocardial Infarction

Intervention

Device:
• Guardian System
There is no intervention in this study. The device is a diagnostic only.

Locations

Country	Name	City	State
United States	Albany Associates in Cardiology	Albany	New York
United States	Cardiology Center of Amarillo	Amarillo	Texas
United States	AnMed Health	Anderson	South Carolina
United States	MedStar Health Research Institute	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	McLaren Bay Region	Bay City	Michigan
United States	Bay Pines VA Healthcare System	Bay Pines	Florida
United States	Suburban Hospital - Johns Hopkins Medicine	Bethesda	Maryland
United States	Cardiology, P.C.	Birmingham	Alabama
United States	Premier Healthcare	Bloomington	Indiana
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Buffalo Heart Group - Mercy Hospital of Buffalo	Buffalo	New York
United States	Buffalo Heart Group - Millard Fillmore Gates Circle Hospital	Buffalo	New York
United States	Northwestern University	Chicago	Illinois
United States	John Muir Clinical Research Center	Concord	California
United States	Innovative Medical Research	Covington	Louisiana
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Daytona Heart Group	Daytona Beach	Florida
United States	DMC Cardiovascular Institute at Harper-Hutzel Hospital	Detroit	Michigan
United States	Detroit Clinical Research Center	Farmington Hills	Michigan
United States	Cardiology Consultants of East Michigan	Flint	Michigan
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Northern Indiana Research Alliance	Fort Wayne	Indiana
United States	Cardiology Associates of Fredericksburg	Fredericksburg	Virginia
United States	NorthFL/South GA VA Health System	Gainesville	Florida
United States	Stern Cardiovascular Center	Germantown	Tennessee
United States	California Clinical Research Foundation	Glendale	California
United States	Genesys Regional Medical Center	Grand Blanc	Michigan
United States	Spectrum Health	Grand Rapids	Michigan
United States	Greenville Hospital System	Greenville	South Carolina
United States	Heart Clinic of Hammond	Hammond	Louisiana
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	West Houston Area Clinical Trial Consultants	Houston	Texas
United States	West Houston Area Clinical Trial Consultants	Houston	Texas
United States	Heart Center Research/Huntsville Hospital	Huntsville	Alabama
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Turkey Creek Medical Center	Knoxville	Tennessee
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	St. Mary Medical Center Research Institute	Langhorne	Pennsylvania
United States	Sparrow Clinical Research Institute	Lansing	Michigan
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	The Medical Center of Central Georgia	Macon	Georgia
United States	Virginia Cardiovascular Associates	Manassas	Virginia
United States	Heart Center of Lake County	Merrillville	Indiana
United States	Banner Heart Hospital	Mesa	Arizona
United States	Mercy Research Institute	Miami	Florida
United States	University of Miami	Miami	Florida
United States	New Phase Clinical Trials	Miami Beach	Florida
United States	Mission Internal Medical Group	Mission Viejo	California
United States	McLaren Macomb	Mount Clemens	Michigan
United States	Medical Consultants, PC	Muncie	Indiana
United States	St. Thomas Research Institute	Nashville	Tennessee
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	University of Medicine & Dentistry NJ	New Brunswick	New Jersey
United States	Complete Cardiology Care	New Smyrna Beach	Florida
United States	Columbia University Medical Center	New York	New York
United States	St. Michael's Medical Center	Newark	New Jersey
United States	Riverside Regional Medical Center	Newport News	Virginia
United States	Sentara Cardiovascular Research Institute	Norfolk	Virginia
United States	South Oklahoma Heart Research	Oklahoma City	Oklahoma
United States	Orange County Heart Institute and Research Center Hospital	Orange	California
United States	Advocate Medical Group	Park Ridge	Illinois
United States	Huntington Memorial Hospital	Pasadena	California
United States	Cardiac & Vascular Research Center of Northern Michigan	Petoskey	Michigan
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Banner Good Samaritan Medical Center	Phoenix	Arizona
United States	Woodholme Cardiovacular Associates	Pikesville	Maryland
United States	Allegheny-Singer Research Institute	Pittsburgh	Pennsylvania
United States	REX Healthcare	Raleigh	North Carolina
United States	Mayo Clinic	Rochester	Minnesota
United States	Sutter Memorial Hospital	Sacramento	California
United States	University of California Davis Medical Center	Sacramento	California
United States	East Coast Institute for Research	Saint Augustine	Florida
United States	Salinas Valley Memorial Hospital	Salinas	California
United States	Radiant Research	Santa Rosa	California
United States	Donald Guthrie Foundation for Education & Research	Sayre	Pennsylvania
United States	Swedish Medical Center/Cardiovascular Research	Seattle	Washington
United States	Louisiana Heart Center	Slidell	Louisiana
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Washington Adventist Hospital	Takoma Park	Maryland
United States	Florida Hospital - Pepin Heart Institute	Tampa	Florida
United States	Univeristy of South Florida	Tampa	Florida
United States	Scott and White Healthcare	Temple	Texas
United States	Cardiovascular Research Center	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Southwest Heart Group	Tucson	Arizona
United States	Tyler Cardiovascular Consultants	Tyler	Texas
United States	Cardiovascular Associates, Ltd	Virginia Beach	Virginia
United States	Lourdes Cardiology Services	Voorhees	New Jersey
United States	Washington Hospital Center	Washington	District of Columbia
United States	Geisinger Wyoming Valley Heart Hospital	Wilkes-Barre	Pennsylvania
United States	Cardiology Group of Western New York	Williamsville	New York
United States	Cardiac Diagnostic Associates/York Hospital	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Angel Medical Systems	Symbios Clinical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	With Amendment the primary efficacy objective was amended to be a co-primary endpoint which included A) a hypothesis test of superiority for positive predictive value of ER visits in the ALARMS_ON group due to Guardian alerting (with or without concurrent symptoms) compared to ER visits in the ALARMS_OFF group due to symptoms only; AND B) a hypothesis test of non-inferiority for rate of false positive ER visits in the ALARMS_ON group due to Guardian alerting (with or without concurrent symptoms) compared to rate of false positive ER visits in the ALARMS_OFF group due to symptoms only.	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	- 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.	With Amendment the secondary efficacy endpoint measures were amended to include Endpoint #1) a hypothesis test of superiority for rate of false positive ER visits in the ALARMS_ON group due to Guardian alerting (with or without concurrent symptoms) compared to rate of false positive ER visits in the ALARMS_OFF group due to symptoms only.	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	Secondary Endpoint #2	With Amendment the secondary efficacy endpoint measures were amended to include Endpoint #2) The number of Silent MIs, the percentage in relation to total MIs in the ALARMS ON group, and the percentage of subjects experiencing Silent MIs will be reported (no hypotheses existed for this endpoint)	With amendment the study period spanned from December 2008 until database lock April 1, 2014.
Secondary	Secondary Endpoint #3	With Amendment the secondary efficacy endpoint measures were amended to include Endpoint #3) Descriptive statistics for the median, average and distribution of symptom-to-door and alarm-to-door times for STEMI events and the number and percentage of subjects with time-to-door times of < 2 hours will be reported for both the ALARMS ON and ALARMS OFF groups (no hypotheses existed for this endpoint).	With amendment the study period spanned from December 2008 until database lock April 1, 2014.
Secondary	Secondary Endpoint #4	With Amendment the secondary efficacy endpoint measures were amended to include Endpoint #4) The time that elapses between the initial patient prompt (alarm or symptom) and arrival at a medical facility will be calculated for all subjects who suffered a STEMI or NSTEMI, and had an associated Guardian alarm (no hypotheses existed for this endpoint).	With amendment the study period spanned from December 2008 until database lock April 1, 2014.
Secondary	Secondary Endpoint #5	With Amendment the secondary efficacy endpoint measures were amended to include Endpoint #5: The time that elapses between the initial patient prompt (Alarm or Symptom) and arrival at a medical facility will be calculated for all subjects who suffered an ACS event (STEMI, NSTEMI, or Unstable Angina), and had an associated Guardian System alarm (with or without symptoms) (no hypotheses existed for this endpoint).	With amendment the study period spanned from December 2008 until database lock April 1, 2014.