ADVANCEIII: Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III

• Sponsor: Medtronic Bakken Research Center (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00617175
• Collaborator: (none)
• Enrollment: 1,902
• Locations: 91
• Arms: 2
• Duration (Months): 47
• Patients Per Site: 20.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

To demonstrate a reduction in the number of ventricular therapies (ATP and Shocks) delivered for treating spontaneous arrhythmia episodes with a fast cycle length (CL≤ 320ms) as a consequence of self-termination and better arrhythmia discrimination due to a greater number of R-R intervals necessary to detect ventricular events.

Condition or Disease	Intervention/Treatment	Phase
Heart Disease	Device: Implantable Defibrillator; Device: Implantable Defibrillator	Phase 4

Detailed Description

Primary Objective:

The primary objective is to demonstrate a 20% reduction of ventricular therapies (ATP and Shocks) delivered for treating spontaneous arrhythmia episodes with a fast cycle length (CL ≤ 320 ms) by choosing a number of 30 out of 40 intervals to detect (NID) compared to a NID of 18 out of 24 in subjects with either Class I or IIA indication for ICD implantation, regardless of cardiac resynchronization capabilities.

Secondary Objectives:

1. Evaluate the percent reduction in the number of shocks delivered per subject for treating spontaneous episodes with a fast cycle length (CL ≤ 320 ms) and for spontaneous ventricular episodes.

2. Evaluate the efficacy of ATP in successfully treating spontaneous ventricular episodes (CL: 200ms-320ms) for subjects in primary and secondary prevention in both arms of the study.

3. Evaluate acceleration rate or degeneration into VF of spontaneous episodes (CL of 200ms-320ms) due to ATP therapy in the two study arms.

4. Compare the likelihood of syncopal events associated with spontaneous episodes with a fast cycle length (CL ≤ 320 ms).

5. Describe the economic impact and the quality of life consequences.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1902 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: ADVANCE III: Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Long NID Programming a number of 30 out of 40 intervals to detect (NID)ventricular arrhythmia	Device: Implantable Defibrillator; Number of 30 out of 40 intervals to detect (NID)Fast Ventricular Tachycardia
Active Comparator: Short NID Programming a number of 18 out of 24 intervals to detect (NID)ventricular arrhythmia	Device: Implantable Defibrillator; number of 18 out of 24 intervals to detect (NID)Fast Ventricular Tachycardia

Outcome Measures

Primary Outcome Measures

1. For the Primary Endpoint the Reduction of Ventricular Therapies (ATP and Shocks) Delivered for Treating Fast Spontaneous Arrhythmia Episodes Was Measured. [From enrollment to study completion or exit whichever occured first]

   for each patient, the exposure time was calculated as the period between randomization and until study completion or exit whichever occured first. Exposure times for all patients were then summed. The rate of therapies was calculated as the sum of all therapies delivered in the study (for each arm) over the sum of exposure times * 100.

Secondary Outcome Measures

1. Evaluate the Percent Reduction in the Number of Shocks Delivered Per Subject for Treating Spontaneous Episodes With a Fast Cycle Length (CL < 320 ms) and for Spontaneous Ventricular Episodes. [end of study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Either ICD or CRT+ICD indications (Class I-IIA) according to the current AHA / ACC / ESC guidelines.

• Previous implant of a Medtronic device including "ATP During Charging" feature for 15 days at the maximum.

Exclusion Criteria:

• ICD replacements and upgrading.

• Brugada Syndrome, Long QT and HCM patients

• Ventricular tachyarrhythmia associated with reversible cause.

• Other electrical implantable devices (Neurostimulators, etc.).

• Subject's life expectancy less than 1 year.

• Subject on heart transplant list which is expected in less than 1 year.

• Subject is <18 years of age, or the subject is under a minimum age that is required as defined by local law

• Women who are pregnant or women of childbearing potential who are not on a reliable form of birth control.

• Unwillingness or inability to provide written informed consent.

• Enrolment in, or intention to participate in, another clinical trial.

• Inaccessibility to come to the study center for the follow-up visits.

• Mechanical tricuspid valve.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hopital St-Joseph	Gilly		Belgium
2	CHU Brugmann	Laken		Belgium
3	CHR La Citadelle Liege	Liege		Belgium
4	CHR Namur	Namur		Belgium
5	AZ Nikolaas	Sint-Niklaas		Belgium
6	KAS Gentofte	Hellerup		Denmark
7	Odense Universitets Hospital	Odense		Denmark
8	Turku University Central Hospital	Turku		Finland
9	Hôpital Michalon- CHU Grenoble	Grenoble		France
10	NCN Nantes	Nantes Cedex 2		France
11	CHU Nantes - Hôpital Guillaume et René Laënnec	Nantes		France
12	Hopital de la Pitie Salpetriere	Paris		France
13	Centre Hospitalier de Pau	Pau		France
14	CHU Hôpital de Pontchaillou Rennes	Rennes		France
15	CH Rangueil Toulouse	Toulouse		France
16	Clinique Pasteur	Toulouse		France
17	RWTH Aachen	Aachen		Germany
18	University of Bonn	Bonn		Germany
19	Kardiologisches Zentrum an der Klinik Rotes Kreuz	Frankfurt am Main		Germany
20	SRH Wald-Klinikum Gera gGmbH	Gera		Germany
21	Universitätskliniken des Saarlandes	Homburg		Germany
22	Klinikum Lüdenscheid	Lüdenscheid		Germany
23	Klinikum Dorothea Christiane Erxleben Quedlinburg	Quedlinburg		Germany
24	Universität Rostock- Medizinische Fakultät	Rostock		Germany
25	Diakoniekrankenhaus Rotenburg	Rotenburg		Germany
26	Semmelweis University AOK	Budapest		Hungary
27	Zala County Hospital	Zalaegerszeg		Hungary
28	Presidio Ospedaliero di Venere	Carbonara	Bari	Italy
29	Azienda.Ospedaliera.G.M. Lancisi	Ancona		Italy
30	Azienda Ospedaliera G. Rummo	Benevento		Italy
31	Cliniche Gavazzeni	Bergamo		Italy
32	Stab. Ospedaliero Di Summa-Perrino - Brindisi	Brindisi		Italy
33	Casa di Cura Mater Domini	Castellanza		Italy
34	Ospedale Pugliese e Ciaccio	Catanzaro		Italy
35	A.O. Santa Croce e Carle	Cuneo		Italy
36	Ente Ospedaliero Ospedali Galliera - Genova	Genova		Italy
37	Ospedale Maggiore di Lodi	Lodi		Italy
38	Istituto Ca' Granda-Niguarda	Milano		Italy
39	San Carlo Borromeo	Milano		Italy
40	Nuovo Osp. Civile S. Agostino	Modena		Italy
41	P.O. di Montebelluna	Montebelluna		Italy
42	Ospedale S. Giacomo	Novi Ligure		Italy
43	Policlinico S. Matteo	Pavia		Italy
44	Osp. S. Maria degli Angeli - Pordenone	Pordenone		Italy
45	Ospedale Misericordia e Dolce	Prato		Italy
46	Azienda Complesso Ospedaliero San Filippo Neri	Roma		Italy
47	Ospedale Sandro Pertini	Roma		Italy
48	Ospedale Sant Eugenio	Roma		Italy
49	Istituto Clinico Humanitas	Rozzano		Italy
50	Osp. S. Giovanni di Dio e Ruggi dAragona	Salerno		Italy
51	AZ. Osp. Ordine Mauriziano	Torino		Italy
52	A.O. S.Maria della Misericordia	Udine		Italy
53	ULSS N.6 S. Bortolo - Vicenza	Vicenza		Italy
54	Medisch Spectrum Twente	Enschede		Netherlands
55	St. Antonius Ziekenhuis Nieuwegein	Nieuwegein		Netherlands
56	Zoz Mswia	Bialystok		Poland
57	Hospital Garcia Orta, SA	Almada		Portugal
58	Hospital de Santa Maria	Lisboa		Portugal
59	Hospital de Santa Marta	Lisboa		Portugal
60	Hospital Geral de Santo António	Porto		Portugal
61	Tyumen Cardiology Center	Tyumen		Russian Federation
62	King Fahd Armed Forces Hospital	Jeddah		Saudi Arabia
63	King Khalid Univ. Hospital - King Saud University	Riyadh		Saudi Arabia
64	Bloemfontein Medi-Clinic	Bloemfontein		South Africa
65	Christiaan Barnard Memorial Hospital	Cape Town		South Africa
66	University of Cape Town - Groote Schuur Hospital	Cape Town		South Africa
67	Vincent Pallotti Hospital	Cape Town		South Africa
68	Milpark Hospital	Johannesburg		South Africa
69	Sunninghill Hospital	Johannesburg		South Africa
70	UNITAS Hospital	Pretoria		South Africa
71	Hospital General Universitario de Alicante	Alicante		Spain
72	Hospital de Basurto - Bilbao	Bilbao		Spain
73	Hospital General Yagüe	Burgos		Spain
74	Hospital General San Pedro de Alcantara	Caceres		Spain
75	Hospital General de Ciudad Real	Ciudad Real		Spain
76	Hospital de Donostia	Donostia-San Sebastian		Spain
77	Hospital Universitario Virgen de las Nieves	Granada		Spain
78	H. Ramón y Cajal	Madrid		Spain
79	Hospital General Universitario Gregorio Marañón	Madrid		Spain
80	Hospital Puerta de Hierro Majadahonda	Madrid		Spain
81	Hospital Universitario La Paz	Madrid		Spain
82	Hospital Clinico de Malaga - Virgen de la Victoria	Malaga		Spain
83	Hospital Universitario Son Dureta	Palma Mallorca		Spain
84	Hospital Universitario de San Juan	San Juan de Alicante		Spain
85	Hospital Ntra. Sra. de la Candelaria	Santa Cruz de Tenerife		Spain
86	Hospital Universitario de Canarias	Santa Cruz de Tenerife		Spain
87	Hospital Virgen de La Salud	Toledo		Spain
88	Hospital Arnau de Vilanova	Valencia		Spain
89	Hospital Clinico Universitario de Valencia	Valencia		Spain
90	Chuvi-Xeral-Cíes	Vigo		Spain
91	Hospital de Txagorritxu	Vitoria / Gasteiz		Spain

Sponsors and Collaborators

• Medtronic Bakken Research Center

Investigators

• Study Chair: Jorg O. Schwab, MD, University of Bonn, Bonn, Germany
• Principal Investigator: Maurizio Gasparini, MD, Humanitas Hospital, Milano Italy
• Principal Investigator: Maurizio Lunati, MD, Niguarda Hospital, Milano, Italy
• Principal Investigator: Bernd Lemke, MD, Klinikum Lüdenscheid, Lüdenscheid, Germany
• Principal Investigator: João Sousa, MD, H. Santa Maria - Lisbon - Portugal
• Principal Investigator: Andrzej Okreglicki, MD, University of Cape Town, Cape Town, South Africa
• Principal Investigator: Angel Arenal, MD, Hospital Gregorio Marañón, Madrid, Spain
• Principal Investigator: Maurits Wijffels, MD, St. Antonius hospital - NIEUWEGEIN, The Netherlands

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medtronic Bakken Research Center
• ClinicalTrials.gov Identifier: NCT00617175
• Other Study ID Numbers: ADVANCE III; ADVANCE III
• First Posted: Feb 15, 2008
• Last Update Posted: Mar 24, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Medtronic Bakken Research Center: Implantable Cardiac Defibrillator; therapies reduction; Shocks; Quality of Life
• Additional relevant MeSH terms: Heart Diseases

Study Results

Participant Flow

Arm/Group Title	Short NID	Long NID
Arm/Group Description	Programming a number of 18 out of 24 intervals to detect (NID)ventricular arrhythmia	Programming a number of 30 out of 40 intervals to detect (NID)ventricular arrhythmia
Period Title: Overall Study
STARTED	954	948
COMPLETED	954	948
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Short NID	Long NID	Total
Arm/Group Description	Programming a number of 18 out of 24 intervals to detect (NID)ventricular arrhythmia	Programming a number of 30 out of 40 intervals to detect (NID)ventricular arrhythmia	Total of all reporting groups
Overall Participants	954	948	1902
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	391 41%	390 41.1%	781 41.1%
>=65 years	563 59%	558 58.9%	1121 58.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.5 (11.1)	65.4 (11.0)	65.47 (11.04)
Sex: Female, Male (Count of Participants)
Female	151 15.8%	153 16.1%	304 16%
Male	803 84.2%	795 83.9%	1598 84%
Region of Enrollment (participants) [Number]
Germany	52 5.5%	60 6.3%	112 5.9%
Spain	196 20.5%	196 20.7%	392 20.6%
Italy	448 47%	429 45.3%	877 46.1%
Hungary	11 1.2%	9 0.9%	20 1.1%
Netherlands	25 2.6%	23 2.4%	48 2.5%
Belgium	18 1.9%	22 2.3%	40 2.1%
France	61 6.4%	62 6.5%	123 6.5%
Russian Federation	9 0.9%	18 1.9%	27 1.4%
Saudi Arabia	45 4.7%	45 4.7%	90 4.7%
Denmark	9 0.9%	14 1.5%	23 1.2%
Finland	3 0.3%	2 0.2%	5 0.3%
South Africa	32 3.4%	24 2.5%	56 2.9%
Poland	22 2.3%	14 1.5%	36 1.9%
Portugal	23 2.4%	30 3.2%	53 2.8%

Outcome Measures

1. Primary Outcome

Title	For the Primary Endpoint the Reduction of Ventricular Therapies (ATP and Shocks) Delivered for Treating Fast Spontaneous Arrhythmia Episodes Was Measured.
Description	for each patient, the exposure time was calculated as the period between randomization and until study completion or exit whichever occured first. Exposure times for all patients were then summed. The rate of therapies was calculated as the sum of all therapies delivered in the study (for each arm) over the sum of exposure times * 100.
Time Frame	From enrollment to study completion or exit whichever occured first

Outcome Measure Data

Analysis Population Description

For the primary endpoint analysis, only patients with at least a device data record were considered.

Arm/Group Title	NID 18/24	NID 30/40
Arm/Group Description	standard number of interval to detect ventricular arrhythmias	Prolonged number of interval to detect ventricular arrhythmias
Measure Participants	891	876
Number (95% Confidence Interval) [rate of therapies per 100 patient-years]	67.1	41.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NID 18/24, NID 30/40
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Negative binomial regression
	Comments

2. Secondary Outcome

Title	Evaluate the Percent Reduction in the Number of Shocks Delivered Per Subject for Treating Spontaneous Episodes With a Fast Cycle Length (CL < 320 ms) and for Spontaneous Ventricular Episodes.
Time Frame	end of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events collection started at day 0 after enrollment until study completion or exit whichever occured first.
Arm/Group Title	Short NID		Long NID
Arm/Group Description	Programming a number of 18 out of 24 intervals to detect (NID)ventricular arrhythmia		Programming a number of 30 out of 40 intervals to detect (NID)ventricular arrhythmia
All Cause Mortality
	Short NID		Long NID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Short NID		Long NID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	300/954 (31.4%)		258/948 (27.2%)
Blood and lymphatic system disorders
Thromboembolic Events	16/954 (1.7%)		8/948 (0.8%)
hypotension	1/954 (0.1%)		1/948 (0.1%)
Hypertension	1/954 (0.1%)		1/948 (0.1%)
Cardiac disorders
Lead Dislodgment	27/954 (2.8%)		20/948 (2.1%)
Worsening heart failure	95/954 (10%)		83/948 (8.8%)
System Dysfunction	1/954 (0.1%)		1/948 (0.1%)
Inappropriate Tachyarrhythmia Therapy	7/954 (0.7%)		5/948 (0.5%)
Acute Myocardial Infarction	9/954 (0.9%)		11/948 (1.2%)
Coronary Artery disease	7/954 (0.7%)		4/948 (0.4%)
Elevated Threshold	4/954 (0.4%)		1/948 (0.1%)
All cause syncope	9/954 (0.9%)		15/948 (1.6%)
Cardiogenic shock	3/954 (0.3%)		3/948 (0.3%)
Ventricular Arrhythmia	24/954 (2.5%)		22/948 (2.3%)
Atrial Arrhthmias	22/954 (2.3%)		15/948 (1.6%)
Angina	6/954 (0.6%)		5/948 (0.5%)
Extracardiac Stimulation	2/954 (0.2%)		3/948 (0.3%)
Dyspnea	2/954 (0.2%)		4/948 (0.4%)
bradycardia	1/954 (0.1%)		0/948 (0%)
General disorders
Neoplasia	19/954 (2%)		8/948 (0.8%)
Musculoskeletal and connective tissue disorders
Musculoskeletal diseases	10/954 (1%)		6/948 (0.6%)
Renal and urinary disorders
Renal Failure	10/954 (1%)		8/948 (0.8%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	6/954 (0.6%)		6/948 (0.6%)
Chronic obstructive pulmonary disease	2/954 (0.2%)		5/948 (0.5%)
Surgical and medical procedures
Pocket Hematoma	3/954 (0.3%)		6/948 (0.6%)
Post Surgical Infection	5/954 (0.5%)		3/948 (0.3%)
epicardial LV implant	0/954 (0%)		1/948 (0.1%)
Pericardial Effusion	1/954 (0.1%)		2/948 (0.2%)
Pocket Infection	11/954 (1.2%)		17/948 (1.8%)
Pneumothorax	1/954 (0.1%)		1/948 (0.1%)
Device migration	1/954 (0.1%)		3/948 (0.3%)
Other (Not Including Serious) Adverse Events
	Short NID		Long NID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/954 (0%)		0/948 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.