ALERTS: AngelMed for Early Recognition and Treatment of STEMI

Sponsor

Angel Medical Systems (Industry)

Overall Status

Completed

CT.gov ID

NCT00781118

Collaborator

Symbios Clinical (Other)

1,020

Enrollment

Locations

Arms

101.5

Actual Duration (Months)

10.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myocardial Infarction (AMI) Coronary Occlusion Acute Coronary Syndrome	Device: Guardian System	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1020 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

AngelMed for Early Recognition and Treatment of STEMI

Actual Study Start Date :

Dec 1, 2008

Actual Primary Completion Date :

May 1, 2014

Actual Study Completion Date :

May 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment The Treatment arm has alerting enabled in their device during the 6-month randomization period. Treatment arm patients also have alerting enabled in the post-randomization period. Once a patient arrives at the ER, the standard of care triage process for MI is followed and that is outside of the ALERTS Study protocol. With Amendment the Treatment arm was re-defined as an ALARMS_ON group which included A) Control patients after the randomization period and until database lock (4/1/2014); and, b) Treatment patients both during the randomization period and after the randomization period until database lock (4/1/2014).	Device: Guardian System There is no intervention in this study. The device is a diagnostic only.
Other: Control The Control arm has alerting disabled in their device during the 6-month randomization period. Control arm patients also have alerting enabled in the post-randomization period. Once a patient arrives at the ER, the standard of care triage process for MI is followed and that is outside of the ALERTS Study protocol. With Amendment the Control arm was re-defined as an ALARMS_OFF group which included A) Control patients during the randomization period when the Guardian did not have alarms enabled.	Device: Guardian System There is no intervention in this study. The device is a diagnostic only.

Arm

Intervention/Treatment

Experimental: Treatment

The Treatment arm has alerting enabled in their device during the 6-month randomization period. Treatment arm patients also have alerting enabled in the post-randomization period. Once a patient arrives at the ER, the standard of care triage process for MI is followed and that is outside of the ALERTS Study protocol. With Amendment the Treatment arm was re-defined as an ALARMS_ON group which included A) Control patients after the randomization period and until database lock (4/1/2014); and, b) Treatment patients both during the randomization period and after the randomization period until database lock (4/1/2014).

Device: Guardian System

There is no intervention in this study. The device is a diagnostic only.

Other: Control

The Control arm has alerting disabled in their device during the 6-month randomization period. Control arm patients also have alerting enabled in the post-randomization period. Once a patient arrives at the ER, the standard of care triage process for MI is followed and that is outside of the ALERTS Study protocol. With Amendment the Control arm was re-defined as an ALARMS_OFF group which included A) Control patients during the randomization period when the Guardian did not have alarms enabled.

Device: Guardian System

There is no intervention in this study. The device is a diagnostic only.

Outcome Measures

Primary Outcome Measures

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. [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.]
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.

Secondary Outcome Measures

- 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. [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.]
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.
Secondary Endpoint #2 [With amendment the study period spanned from December 2008 until database lock April 1, 2014.]
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)
Secondary Endpoint #3 [With amendment the study period spanned from December 2008 until database lock April 1, 2014.]
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).
Secondary Endpoint #4 [With amendment the study period spanned from December 2008 until database lock April 1, 2014.]
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).
Secondary Endpoint #5 [With amendment the study period spanned from December 2008 until database lock April 1, 2014.]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject has at least one of the following conditions:

Diabetes (Type I or Type II)
Compromised renal function (Cr > 1.2 mg/dl or creatinine clearance less than 50)
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:

Post-menopause or amenorrheic during the past year
Surgical sterilization
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology, P.C.	Birmingham	Alabama	United States	35211
2	Heart Center Research/Huntsville Hospital	Huntsville	Alabama	United States	35801
3	Banner Heart Hospital	Mesa	Arizona	United States	85206
4	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
5	Southwest Heart Group	Tucson	Arizona	United States	85710
6	John Muir Clinical Research Center	Concord	California	United States	94520
7	California Clinical Research Foundation	Glendale	California	United States	91204
8	Long Beach Memorial Medical Center	Long Beach	California	United States	90806
9	Mission Internal Medical Group	Mission Viejo	California	United States	92691
10	Orange County Heart Institute and Research Center Hospital	Orange	California	United States	92868
11	Huntington Memorial Hospital	Pasadena	California	United States	91105
12	University of California Davis Medical Center	Sacramento	California	United States	95817
13	Sutter Memorial Hospital	Sacramento	California	United States	95819
14	Salinas Valley Memorial Hospital	Salinas	California	United States	93901
15	Radiant Research	Santa Rosa	California	United States	95405
16	Washington Hospital Center	Washington	District of Columbia	United States	20010
17	Bay Pines VA Healthcare System	Bay Pines	Florida	United States	33744
18	Daytona Heart Group	Daytona Beach	Florida	United States	32114
19	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
20	NorthFL/South GA VA Health System	Gainesville	Florida	United States	32608
21	New Phase Clinical Trials	Miami Beach	Florida	United States	33140
22	Mercy Research Institute	Miami	Florida	United States	33133
23	University of Miami	Miami	Florida	United States	33136
24	Complete Cardiology Care	New Smyrna Beach	Florida	United States	32169
25	East Coast Institute for Research	Saint Augustine	Florida	United States	32086
26	Univeristy of South Florida	Tampa	Florida	United States	33606
27	Florida Hospital - Pepin Heart Institute	Tampa	Florida	United States	33613
28	The Medical Center of Central Georgia	Macon	Georgia	United States	31201-2102
29	Northwestern University	Chicago	Illinois	United States	60611
30	Advocate Medical Group	Park Ridge	Illinois	United States	60068
31	Premier Healthcare	Bloomington	Indiana	United States	47403
32	Northern Indiana Research Alliance	Fort Wayne	Indiana	United States	46804
33	Heart Center of Lake County	Merrillville	Indiana	United States	46410
34	Medical Consultants, PC	Muncie	Indiana	United States	47303
35	Central Baptist Hospital	Lexington	Kentucky	United States	40503
36	Innovative Medical Research	Covington	Louisiana	United States	70433
37	Heart Clinic of Hammond	Hammond	Louisiana	United States	70403
38	Louisiana Heart Center	Slidell	Louisiana	United States	70433
39	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
40	MedStar Health Research Institute	Baltimore	Maryland	United States	21239
41	Suburban Hospital - Johns Hopkins Medicine	Bethesda	Maryland	United States	20814
42	Woodholme Cardiovacular Associates	Pikesville	Maryland	United States	21208
43	Washington Adventist Hospital	Takoma Park	Maryland	United States	20912
44	McLaren Bay Region	Bay City	Michigan	United States	48708
45	DMC Cardiovascular Institute at Harper-Hutzel Hospital	Detroit	Michigan	United States	48201
46	Detroit Clinical Research Center	Farmington Hills	Michigan	United States	48334
47	Cardiology Consultants of East Michigan	Flint	Michigan	United States	48532
48	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
49	Spectrum Health	Grand Rapids	Michigan	United States	49503
50	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
51	Sparrow Clinical Research Institute	Lansing	Michigan	United States	48912
52	McLaren Macomb	Mount Clemens	Michigan	United States	48043
53	Cardiac & Vascular Research Center of Northern Michigan	Petoskey	Michigan	United States	49770
54	Mayo Clinic	Rochester	Minnesota	United States	55905
55	Jersey Shore University Medical Center	Neptune	New Jersey	United States	07754
56	University of Medicine & Dentistry NJ	New Brunswick	New Jersey	United States	08901
57	St. Michael's Medical Center	Newark	New Jersey	United States	07102
58	Lourdes Cardiology Services	Voorhees	New Jersey	United States	08043
59	Albany Associates in Cardiology	Albany	New York	United States	12205
60	SUNY Downstate Medical Center	Brooklyn	New York	United States	11203
61	Buffalo Heart Group - Mercy Hospital of Buffalo	Buffalo	New York	United States	14215
62	Buffalo Heart Group - Millard Fillmore Gates Circle Hospital	Buffalo	New York	United States	14215
63	Columbia University Medical Center	New York	New York	United States	10032
64	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
65	Cardiology Group of Western New York	Williamsville	New York	United States	14221
66	REX Healthcare	Raleigh	North Carolina	United States	27607
67	Good Samaritan Hospital	Dayton	Ohio	United States	45406
68	Cardiovascular Research Center	Toledo	Ohio	United States	43608
69	University of Toledo	Toledo	Ohio	United States	43614
70	South Oklahoma Heart Research	Oklahoma City	Oklahoma	United States	73135
71	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
72	Penn State Hershey Medical Center	Hershey	Pennsylvania	United States	17033
73	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17602
74	St. Mary Medical Center Research Institute	Langhorne	Pennsylvania	United States	19047
75	Drexel University College of Medicine	Philadelphia	Pennsylvania	United States	19102
76	Allegheny-Singer Research Institute	Pittsburgh	Pennsylvania	United States	15212
77	Donald Guthrie Foundation for Education & Research	Sayre	Pennsylvania	United States	18840
78	Geisinger Wyoming Valley Heart Hospital	Wilkes-Barre	Pennsylvania	United States	18711
79	Cardiac Diagnostic Associates/York Hospital	York	Pennsylvania	United States	17405
80	AnMed Health	Anderson	South Carolina	United States	29621
81	Greenville Hospital System	Greenville	South Carolina	United States	29605
82	Stern Cardiovascular Center	Germantown	Tennessee	United States	38138
83	Turkey Creek Medical Center	Knoxville	Tennessee	United States	37934
84	St. Thomas Research Institute	Nashville	Tennessee	United States	37203
85	Cardiology Center of Amarillo	Amarillo	Texas	United States	79106
86	West Houston Area Clinical Trial Consultants	Houston	Texas	United States	77008
87	West Houston Area Clinical Trial Consultants	Houston	Texas	United States	77094
88	Scott and White Healthcare	Temple	Texas	United States	76502
89	Tyler Cardiovascular Consultants	Tyler	Texas	United States	75701
90	Cardiology Associates of Fredericksburg	Fredericksburg	Virginia	United States	22408
91	Virginia Cardiovascular Associates	Manassas	Virginia	United States	20109
92	Riverside Regional Medical Center	Newport News	Virginia	United States	23601
93	Sentara Cardiovascular Research Institute	Norfolk	Virginia	United States	23507
94	Cardiovascular Associates, Ltd	Virginia Beach	Virginia	United States	23462
95	Swedish Medical Center/Cardiovascular Research	Seattle	Washington	United States	98122