Berlin PRehospital Or Usual Delivery of Acute Stroke Care (B_PROUD)

Berlin PRehospital Or Usual Delivery of Acute Stroke Care - Functional Outcomes After Advanced Prehospital Stroke Care

Prehospital stroke care in specialized ambulances increases thrombolysis rates, reduces alarm-to-treatment times, and improves prehospital triage. Preliminary analyses suggest cost-effectiveness. However, scientific proof of improved functional outcome compared to usual care is still lacking. The objective of this trial is to show improved functional outcomes after deployment of the Stroke Emergency Mobile (STEMO) compared to regular care.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Procedure: STEMO; Procedure: Regular care

Detailed Description

This is a pragmatic, prospective, multi-center trial with blinded outcome assessment of treatment candidates three months after stroke. Treatment candidates will be defined as patients with final discharge diagnosis of cerebral ischemia, and onset-to-alarm time ≤4 hours, symptoms not resolved at time of ambulance arrival, and able to walk without assistance prior to emergency. These patients will be included if their emergency call from a predefined catchment area in Berlin, Germany, caused a stroke alarm at the dispatch center during STEMO hours (7am-11pm, Monday-Sunday). About 45% of STEMO dispatches will be handled by regular ambulances since STEMO will be already in operation creating the quasi-randomized control group.

B_PROUD uses data from the B-SPATIAL registry. The B-SPATIAL registry has started recruitment in January 2016. However, B_PROUD recruits patients with symptom onset October 1st, 2016 or later (because data access at the dispatch center had to be established first).

• Study Type: Interventional
• Enrollment (Actual): 1500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Charité

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:

1. Suspected acute stroke according to the dispatcher stroke identification algorithm during STEMO hours (7am-11pm, Monday-Sunday) and within the STEMO catchment area

   Inclusion criteria for primary study population:

2. Final diagnosis of ischemic stroke (ICD 10: I63) or TIA (ICD 10: G45 except G45.4)
3. Confirmed onset-to-alarm time ≤ 4 hours at dispatch
4. Pre-stroke modified Rankin scale ≤ 3 (being able to ambulate, in routine clinical care, patients with mRS up to 3 are usually deemed suitable for tissue plasminogen activator treatment)

Exclusion criteria:

1. Symptom remission until arrival of emergency medical service

2. Malignant or other severe primary disease with life expectancy < 1 year

   Exclusion criteria for primary study population:

3. Major surgery within 4 weeks before study inclusion
4. Confirmed stroke within 3 months before study inclusion
5. Absolute contraindications for thrombolysis AND thrombectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: STEMO deployment; STEMO is a specialized stroke ambulance providing prehospital neurovascular expertise, a CT scanner, point-of-care testing, and telemedical support.	Procedure: STEMO; STEMO, the intervention, includes prehospital neurological emergency assessment with the option to perform CT and CT-angiography, start specialized treatment at the door-step of the patient's house, including thrombolysis with tissue Plasminogen Activator and blood pressure Management (choice of drug at discretion of treating physician), use telemedicine for further expertise as well as results of point-of-care laboratory, prenotification (e.g. for endovascular treatment), triage and transport.
Active Comparator: Regular care; Regular prehospital care consists of an ambulance. In suspected life-threatening cases an emergency physician is sent to the emergency scene in parallel.	Procedure: Regular care; A regular ambulance, the comparator intervention, not equipped with advanced point-of-care laboratory or CT scanner, without telemedicine and not staffed with a neurologist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale	Assessment of functional outcome over the entire range of the modified Rankin Scale	3 months
Co-primary 3-Month Outcome	The co-primary 3-month outcome includes the following range of outcomes: mRS 1-3 if available; mRS 4-5 or (if mRS is missing) living in institution (information according registration office at 4 month after stroke); death. We will run a sensitivity analysis with the co-primary outcome and calculating all patients with missing mRS but still living under private address as mRS 1-3. The latter will help us to include information of patients still living at home but without mRS follow-up. All outcomes will be calculated with ordinal logistic regression.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombolysis rate		3 months
Thrombectomy rate		3 months
Diagnosis and treatment times (A)	Onset-to-treatment time	3 months
Diagnosis and treatment times (B)	onset-to-reperfusion time (for thrombectomy)	3 months
Diagnosis and treatment times (C)	alarm-to-imaging time	3 months
Diagnosis and treatment times (D)	alarm-to-treatment time	3 months
Diagnosis and treatment times (E)	imaging-to-treatment time	3 months
Cost-effectiveness (A)	Additional costs due to implementation and running of STEMO	3 months
Cost-effectiveness (B)	duration of hospital stay regarding acute treatment and rehabilitation	3 months
Cost-effectiveness (C)	hospital related costs	3 months
Cost-effectiveness (D)	costs of long-term care	3 months
Cost-effectiveness (E)	Additional costs due to implementation and running of STEMO, duration of hospital stay regarding acute treatment and rehabilitation, hospital related costs, costs of long-term care	3 months
Quality of life	Assessment with European Quality of Life - 5 Dimensions (EQ-5D) in yearly intervals over 5 years to follow-up	Up to 5 years
Modified Rankin Scale shift analyses	Shift analyses for mRS ≤ 1 at 3 months in patients ≤ 80 years of age living at home without disability and mRS ≤ 2 at 3 months in patients > 80 years of age living at home with help or living in an institution	3 months
In-hospital mortality	Frequency of patients dying within the duration of the hospital stay after admission for stroke.	7 days
Death rate over time	Deaths over time will be determined and compared between groups using a Kaplan-Meier plot	3 months
Discharge status	Including in-hospital mortality among patients not included in the primary study population (patients with intracranial hemorrhages as well as patients receiving thrombolysis in stroke mimics)	3 months
Modified Rankin Scale in patients with intracranial hemorrhages	Assessment of functional outcome among patients with intracranial hemorrhages	3 months
Rate of emergency medical service deliveries to specialized facilities	Assessment for patients with acute ischemic stroke to hospitals with Stroke Unit, for patients with cerebral artery occlusion (internal carotid artery, M1 or proximal M2 segment of middle cerebral artery) to hospitals with thrombectomy facility, and for patients with intracerebral hemorrhage to hospitals with neurosurgery department.	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic hemorrhage (A)	According to NINDS definition after 36 hours in patients receiving thrombolysis or thrombectomy	3 months
Symptomatic hemorrhage (B)	According to ECASS III definitions after 36 hours in patients receiving thrombolysis or thrombectomy	3 months

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Center for Stroke Research Berlin
• Investigators: Principal Investigator: Heinrich Audebert, MD, Charité

Publications and helpful links

General Publications

• Ebinger M, Winter B, Wendt M, Weber JE, Waldschmidt C, Rozanski M, Kunz A, Koch P, Kellner PA, Gierhake D, Villringer K, Fiebach JB, Grittner U, Hartmann A, Mackert BM, Endres M, Audebert HJ; STEMO Consortium. Effect of the use of ambulance-based thrombolysis on time to thrombolysis in acute ischemic stroke: a randomized clinical trial. JAMA. 2014 Apr 23-30;311(16):1622-31. doi: 10.1001/jama.2014.2850.
• Krebes S, Ebinger M, Baumann AM, Kellner PA, Rozanski M, Doepp F, Sobesky J, Gensecke T, Leidel BA, Malzahn U, Wellwood I, Heuschmann PU, Audebert HJ. Development and validation of a dispatcher identification algorithm for stroke emergencies. Stroke. 2012 Mar;43(3):776-81. doi: 10.1161/STROKEAHA.111.634980. Epub 2012 Jan 5.
• Ebinger M, Fiebach JB, Audebert HJ. Mobile computed tomography: prehospital diagnosis and treatment of stroke. Curr Opin Neurol. 2015 Feb;28(1):4-9. doi: 10.1097/WCO.0000000000000165.
• Wendt M, Ebinger M, Kunz A, Rozanski M, Waldschmidt C, Weber JE, Winter B, Koch PM, Freitag E, Reich J, Schremmer D, Audebert HJ; STEMO Consortium. Improved prehospital triage of patients with stroke in a specialized stroke ambulance: results of the pre-hospital acute neurological therapy and optimization of medical care in stroke study. Stroke. 2015 Mar;46(3):740-5. doi: 10.1161/STROKEAHA.114.008159. Epub 2015 Jan 29.
• Kunz A, Ebinger M, Geisler F, Rozanski M, Waldschmidt C, Weber JE, Wendt M, Winter B, Zieschang K, Fiebach JB, Villringer K, Erdur H, Scheitz JF, Tutuncu S, Bollweg K, Grittner U, Kaczmarek S, Endres M, Nolte CH, Audebert HJ. Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study. Lancet Neurol. 2016 Sep;15(10):1035-43. doi: 10.1016/S1474-4422(16)30129-6. Epub 2016 Jul 16.
• Ebinger M, Harmel P, Nolte CH, Grittner U, Siegerink B, Audebert HJ. Berlin prehospital or usual delivery of acute stroke care - Study protocol. Int J Stroke. 2017 Aug;12(6):653-658. doi: 10.1177/1747493017700152. Epub 2017 Mar 22.
• Kunz A, Nolte CH, Erdur H, Fiebach JB, Geisler F, Rozanski M, Scheitz JF, Villringer K, Waldschmidt C, Weber JE, Wendt M, Winter B, Zieschang K, Grittner U, Kaczmarek S, Endres M, Ebinger M, Audebert HJ. Effects of Ultraearly Intravenous Thrombolysis on Outcomes in Ischemic Stroke: The STEMO (Stroke Emergency Mobile) Group. Circulation. 2017 May 2;135(18):1765-1767. doi: 10.1161/CIRCULATIONAHA.117.027693. No abstract available.

Helpful Links

• Prehospital Thrombolysis: A Manual from Berlin (2013)

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): October 24, 2019
• Study Completion (Actual): October 24, 2019

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 15, 2016
• First Posted (Estimate): August 16, 2016

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: thrombolysis; stroke; endovascular treatment; telemedicine; functional outcome; thrombectomy; prehospital
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: B_PROUD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No