Intensified Secondary Prevention Intending a Reduction of Recurrent Events in TIA and Minor Stroke Patients (INSPiRE-TMS)

Intensified Secondary Prevention Intending a Reduction of Recurrent Events in TIA and Minor Stroke Patients (INSPiRE-TMS) A Randomized Trial Comparing a Patient Centered Support Program Versus Conventional Car

Patients after TIA or Stroke are at high risk of experiencing a new stroke or myocardial infarction. Poor adherence to evidence based secondary prevention regimens is frequently seen. Support programs for patients may not only improve adherence to recommended therapies but also reduce the recurrence rate of stroke and heart attack. The investigators hypothesize that compared to regular care, a structured and patient centered secondary prevention program will lead to a relative risk reduction of at least 28% of recurrent vascular events.

Study Overview

• Status: Completed
• Conditions: Mini-Stroke
• Intervention / Treatment: Behavioral: Patient centered structured support program

Detailed Description

Although effective methods of secondary prevention after stroke or TIA are available, adherence to recommended evidence-based treatments is often poor. Programs for supported secondary prevention after cerebrovascular events with improved health education are promising but have not been evaluated regarding recurrent event reduction so far.

A prospective randomized trial has been started to assess the effectiveness of a patient centered structured support program intending a reduction of recurrent vascular events. Usual care consists of structured information given at discharge as well as regular outpatient care by general practitioners. The support program additionally employs a stepwise intensified support program with up to eight appointments over two years in outpatient clinics. Results of risk factor measurements and assessed adherence to medical recommendations are shared with the patients. They are also offered assistance in finding appropriate physical activities or smoking cessation programs.

Patients are randomized to regular care or regular care plus support program and will be followed-up until the total number of 317 primary endpoints has been reached. The composite primary endpoint consists of stroke, major coronary event and vascular death.

• Study Type: Interventional
• Enrollment (Actual): 2082
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12200
    • Dept. of Neurology, Charité Universitätsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute cerebrovascular event (either TIA or minor Stroke within 14 days before study inclusion) according to the following definitions:
• TIA (clinical restitution within 24 hours and ABCD2-Score ≥3) or visible DWI-lesion in MRI
• Minor stroke (mRankin ≤2 at time of inclusion)
• Patients with at least one of the following treatable risk factors:
• Arterial Hypertension
• Diabetes mellitus
• Atrial Fibrillation
• Smoking
• Written informed consent prior to study inclusion
• Realistic perspective in keeping the outpatient appointments

Exclusion Criteria:

• Distance from home to study center not in suitable range for keeping the outpatient appointments
• cognitive impairment jeopardizing adherence to the support program
• Modified Rankin Score >2 at time of study inclusion
• Malignant disease with life expectancy of less than 3 years
• relevant alcohol or other substance abuse (except for nicotine)
• Stroke or TIA etiology without options for evidence based secondary prevention (e.g. dissection or vasculitis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Regular care; Consisting of structured information given at hospital discharge regarding stroke etiology and recommended secondary prevention plus regular outpatient care by general practitioners or family doctors.
Active Comparator: Support program; In addition to regular care: Up to 8 appointments in outpatient clinics. Results of risk factor measurements and assessed adherence to medical recommendations are shared with the patients. In case that a patients fails to meet target values, preventive measures will be modified directly or via recommendation to GPs / family doctors. Patients are also offered assistance in finding appropriate physical activities or smoking cessation programs.	Behavioral: Patient centered structured support program; Behavioural: Structured support program Program with up to 8 outpatient appointments focusing on: Measurement of risk factors; Assessment of medication intake; Monitoring of antithrombotic therapy; Joint agreement of an individual target plan Target values for risk factors: Blood pressure < 140/85 mmHg (<130/80 in diabetics), normal circadian profile; HbA1c <7.5%; Nicotine abstinence; LDL < 100mg/dl (< 70mg/dl in high risk patients); Physical activity ≥ 30min >2 x / week Targets for pharmaceutical treatment: Platelet inhibitors for strokes / TIA of arterial etiology; Combined platelet inhibition over 3 months in symptomatic intra- or extracranial stenosis; Cumarins (INR 2-3) or new oral anticoagulants in AF patients; Statin treatment in patients with LDL >100mg/dl Intervention strategies: • According to Motivational Interviewing; Other Names: Intensified secondary prevention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major vascular event consisting of nonfatal stroke, nonfatal major coronary event and vascular death	Stroke: Acute (focal-) neurological syndrome, caused by brain infarction or intracerebral hemorrhage Major coronary event:Including instable Angina pectoris, STEMI and non-STEMI Vascular death: Caused by stroke (within 30 days of event), or major coronary event (within 7 days of event), or non-cerebral hemorrhage, or by peripheral arterial disease 30 days after vascular event or vascular intervention (intraarterial or surgical), or by pulmonary embolism or sudden death if death occurs within 24 hours in a patients with previously stable and healthy state if no non-vascular cause is documented	Up to 6 years from inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non vascular death		Participants will be followed-up for an average of approximately 3.5 years
Other vascular diseases leading to hospital admission (excl. primary outcome measure)	Consisting of TIA, Angina pectoris, PAD with vascular intervention	Participants will be followed-up for an average of approximately 3.5 years
All hospital admissions with vascular intervention (intraarterial or surgical)		Participants will be followed-up for an average of approximately 3.5 years
Bleedings	All bleedings leading to therapeutic intervention (categorized according to GUSTO definitions)	Participants will be followed-up for an average of approximately 3.5 years
Level of dependency	Assessment according to modified Rankin Score and level of care (German care insurance)	Up to 6 years from inclusion
All hospital admissions		Participants will be followed-up for an average of approximately 3.5 years
Days alive and at home		Participants will be followed-up for an average of approximately 3.5 years

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Aarhus University Hospital; University of Erlangen-Nürnberg Medical School; Klinikum Ludwigshafen; Technical University of Munich; Technische Universität Berlin; Vivantes Clinic Neukölln; Praxis für Neurologie und Psychiatrie am Prinzregentenplatz, München; Vivantes Auguste-Viktoria-Klinikum
• Investigators: Principal Investigator: Heinrich J Audebert, MD, Center for Stroke Research, Charité Universitaetsmedizin Berlin

Publications and helpful links

General Publications

• Ihl T, Ahmadi M, Laumeier I, Steinicke M, Ferse C, Klyscz P, Endres M, Hastrup S, Poppert H, Palm F, Kandil FI, Weber JE, von Weitzel-Mudersbach P, Wimmer MLJ, Audebert HJ. Patient-Centered Outcomes in a Randomized Trial Investigating a Multimodal Prevention Program After Transient Ischemic Attack or Minor Stroke: The INSPiRE-TMS Trial. Stroke. 2022 Sep;53(9):2730-2738. doi: 10.1161/STROKEAHA.120.037503. Epub 2022 Jun 15.
• Ahmadi M, Laumeier I, Ihl T, Steinicke M, Ferse C, Endres M, Grau A, Hastrup S, Poppert H, Palm F, Schoene M, Seifert CL, Kandil FI, Weber JE, von Weitzel-Mudersbach P, Wimmer MLJ, Algra A, Amarenco P, Greving JP, Busse O, Kohler F, Marx P, Audebert HJ. A support programme for secondary prevention in patients with transient ischaemic attack and minor stroke (INSPiRE-TMS): an open-label, randomised controlled trial. Lancet Neurol. 2020 Jan;19(1):49-60. doi: 10.1016/S1474-4422(19)30369-2. Epub 2019 Nov 7.
• Leistner S, Michelson G, Laumeier I, Ahmadi M, Smyth M, Nieweler G, Doehner W, Sobesky J, Fiebach JB, Marx P, Busse O, Kohler F, Poppert H, Wimmer ML, Knoll T, Von Weitzel-Mudersbach P, Audebert HJ. Intensified secondary prevention intending a reduction of recurrent events in TIA and minor stroke patients (INSPiRE-TMS): a protocol for a randomised controlled trial. BMC Neurol. 2013 Jan 24;13:11. doi: 10.1186/1471-2377-13-11.
• Leistner S, Benik S, Laumeier I, Ziegler A, Nieweler G, Nolte CH, Heuschmann PU, Audebert HJ. Secondary prevention after minor stroke and TIA - usual care and development of a support program. PLoS One. 2012;7(12):e49985. doi: 10.1371/journal.pone.0049985. Epub 2012 Dec 17.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: April 23, 2012
• First Submitted That Met QC Criteria: April 26, 2012
• First Posted (Estimate): April 27, 2012

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Stroke, TIA, secondary prevention, support program, multifactorial intervention
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: EA2/084/11