NCT00359203

Brief Summary

ISSUE 3 is a multi-center, prospective, randomised controlled double-blind study aimed to assess the effectiveness of pacemaker therapy for prevention of asystolic neurally-mediated syncope.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
511

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Sep 2006

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 31, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 1, 2006

Completed
1 month until next milestone

Study Start

First participant enrolled

September 1, 2006

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2011

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2012

Completed
1 year until next milestone

Results Posted

Study results publicly available

November 18, 2013

Completed
Last Updated

July 18, 2025

Status Verified

September 1, 2015

Enrollment Period

5 years

First QC Date

July 31, 2006

Results QC Date

May 22, 2013

Last Update Submit

June 30, 2025

Conditions

Syncope

Keywords

syncopeimplantable loop recorder

Outcome Measures

Primary Outcomes (1)

  • Syncope Recurrence Rate

    Intention to treat analysis of percentage of patients with syncope recurrence at 2 years follow-up after study arm assignement

    2 years

Study Arms (2)

Dual chamber pacemaker

PLACEBO COMPARATOR

Dual chamber pacemaker programmed ODO (switched OFF)

Device: Dual chamber pacemeker

Dual chamber pacemeker

ACTIVE COMPARATOR

Medtronic dual chamber pacemaker programmed ON and with Rate Drope Response programmed ON

Device: Dual chamber pacemeker

Interventions

Dual chamber pacemekerDEVICE
Also known as: Any model of Medtronic pacemakers with Rate Drop Respons algorhythm:, K700, K900, Enpulse, Advisa, Versa
Dual chamber pacemakerDual chamber pacemeker

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Suspected or certain neurally-mediated syncope, based on the Guidelines recently published by the Task Force on Syncope of the European Society of Cardiology 2,3 (Appendix 1);
  • More than 3 syncope episodes in the last 2 years;
  • Clinical presentation of syncope of sufficient severity requiring treatment initiation in the physician's and patient's judgement.
  • Age \> 40 years.
  • Negative carotid sinus massage.
  • Patients accept to have an ILR implantation.

You may not qualify if:

  • Carotid sinus hypersensitivity
  • Suspected or certain heart disease and high likelihood of cardiac syncope:
  • Symptomatic orthostatic hypotension diagnosed by standing blood pressure measurement;
  • Loss of consciousness different from syncope (e.g. epilepsy, psychiatric, metabolic, drop-attack, TIA, intoxication, cataplexy);
  • Subclavian steal syndrome;
  • Psychologically or physically (due to any other illness) or cognitively unfit for participation in the study according to the opinion of the investigator;
  • Patient compliance doubtful;
  • Patient geographically or otherwise inaccessible for follow-up;
  • Patient unwilling or unable to give informed consent;
  • Life expectancy \<1 year.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medtronic Italia S.p.A.

Rome, 00165, Italy

Location

Related Publications (1)

  • Brignole M, Menozzi C, Moya A, Andresen D, Blanc JJ, Krahn AD, Wieling W, Beiras X, Deharo JC, Russo V, Tomaino M, Sutton R; International Study on Syncope of Uncertain Etiology 3 (ISSUE-3) Investigators. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial. Circulation. 2012 May 29;125(21):2566-71. doi: 10.1161/CIRCULATIONAHA.111.082313. Epub 2012 May 7.

    PMID: 22565936DERIVED

Related Links

MeSH Terms

Conditions

Syncope

Condition Hierarchy (Ancestors)

UnconsciousnessConsciousness DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Silvia Giuli
Organization
Medtronic Italia SpA
silvia.giuli@medtronic.com
003932814224

Study Officials

  • Michele Brignole, MD

    Ospedali del Tigullio, Lavagna

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 31, 2006

First Posted

August 1, 2006

Study Start

September 1, 2006

Primary Completion

September 1, 2011

Study Completion

November 1, 2012

Last Updated

July 18, 2025

Results First Posted

November 18, 2013

Record last verified: 2015-09

Locations

IT(1)