Optimal Post Tpa-Iv Monitoring in Ischemic Stroke

Acute Ischemic Stroke Patients Receiving Reperfusion Therapy Clinical Trial

Official title:

Optimal Post Tpa-Iv Monitoring in Ischemic Stroke

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03734640
• Other study ID #: OPTIMISTmain
• Status: Recruiting
• Phase: N/A
• Start date: April 28, 2021
• Est. completion date: March 1, 2025

Study information

• Verified date: August 2023
• Source: The George Institute for Global Health, China
• Contact: Craig Anderson, PhD
• Phone: +61 410476311
• Email: canderson[@]georgeinstitute.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

OPTIMISTmain is an investigator-initiated and conducted, international, multicentre, stepped wedge cluster randomized controlled trial comparing the effects of different intensities of nursing care monitoring for patients with acute ischemic stroke of mild severity and without critical care needs after IV-tPA.

Description:

Research question: Patients receiving thrombolytic therapy (tissue plasminogen activator [tPA]) for acute ischaemic stroke (AIS), have been monitored with a high intensity schedule of vital signs and neurologic assessments, which often requires 1:1 nursing and/or admission in an intensive care unit (ICU) or similar ward for at least 24 hours after receiving tPA. Studies indicate that patients with mild degrees of AIS after tPA do not require such intensive monitoring, yet most stroke services continue to follow a practice recommended in guidelines based on the initial cautious evaluation of tPA in AIS over 20 years ago.

Design: Stepped-wedge cluster randomised design. With 3 groups and 4 phases. All groups starting with standard care and in each subsequent phase, groups I through III will switch to the intervention (low-intensity monitoring).

Study centers: This is a global study. Approximately 157 hospitals ('sites') in Australasia, Europe, South American, and North American regions, who are willing to accept the randomized intervention change and adhere to the protocol, collect a required minimum data set on patients over 7 days in hospital (or discharge or death, if sooner), and record any serious adverse event (SAE) during and at clinical outcome assessed at 90 days of follow-up of patients.

Consent/randomization: Hospitals will be eligible if they are using the proposed low-intensity nursing monitoring strategy. A stepped-wedge cluster randomized design has been chosen to avoid contamination, facilitate hospital-wide implementation, and maximize adherence, as the intervention under investigation is to become usual standard of care. The process of one direction (from control to intervention) is to facilitate the low intensity monitoring protocol being applied in clinical practice. The stepped-wedge design means that all hospitals will be randomly allocated to 3 groups: in phase 1, all hospitals will be observed under standard care 'control' conditions according to guideline recommended monitoring; in phase 2, the first cluster of hospitals (Group I) will start receiving the intervention (low-intensity), and then sequentially, Groups II and III will start receiving the interventional package in phase 3 and 4, respectively, so that by phase 4, all hospitals will have the intervention. Those hospitals in Group I are exposed to the intervention for longest time, and those in Group III, the shortest time.

In each phase, hospitals are to maintain a register of all thrombolyzed AIS patients, and to identify all those eligible for, or excluded from participating in the study. Hospitals are required to manage at minimum target of at least 10 consecutive thrombolyzed AIS patients who fulfill the eligibility criteria (presumed 50% of all thrombolyzed AIS patients) over each 4 month period. The recruitment number will vary from 10 to 30 patients, according to seasonal fluctuation and overall numbers of thrombolyzed AIS patients across hospitals. The target number and time limits for each phase will be pre-determined and agreed to with each hospital, to ensure an orderly completion of the study.

On average, for Group I, the time for initiation of the low-intensive intervention is 4 months after activation into phase 1 of the study; for Groups II and III, the time periods for initiation of the low-intensive intervention are 6 and 9 months, after activation, respectively. Data collection will occur at baseline, the first 24 hours, Day 7 (or death or time of hospital discharge, if earlier), and at 90 days (end of follow-up). Patients will be asked to consent to being contacted at some future date to examine long-term outcomes, according to available resources.

A senior executive officer at each center will act as a 'guardian', to provide consent at an institutional level for the intervention to be applied as a 'low risk' intervention to clusters of patients as part of routine care; and written informed consent is to be subsequently obtained from participants, or their approved surrogates, for collection of medical data and participation in the follow-up assessments Randomized allocation of intervention will be assigned by a statistician not otherwise involved in the study according to a statistical program stratified by the country of the site.

Sample size: The sample size required to detect a plausible treatment effect on a clinical outcome in a stepped-wedge trial (3 groups, 4 phases) is 157 hospitals, each recruiting an average of 80 patients (20 per phase), for a total of 12,394 AIS patients. The basis of this calculation is that the study is designed with 90% power (one-sided α = 0.025) to detect non-inferiority (non-inferiority OR margin is 1.25, presumed actual OR is 1.0; the proportion of a bad outcome [mRS 2-6] is 50%) of low-intensity monitoring on the primary outcome. Assuming a stepped-wedge trial of 3 groups and 4 phases, 157 hospitals are required to be randomized into 3 groups of 53 hospitals, each recruiting an average of 16 patients per phase, for a total of 9340 subjects. Assuming 10% with missing primary endpoint data and 5% with nonadherence to randomized treatment, the overall sample size increases to an average of 20 subjects per hospital per phase (i.e. total sample size of 12,394 AIS patients). Allowance will be made to include some very large hospitals (10%, 7) to recruit 50 patients per phase, and smaller hospitals (10%, 7) to recruit 8 patients per phase, in order to allow a broad range of hospitals with variable experience and systems of care for the management of AIS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 7200
• Est. completion date: March 1, 2025
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adults (age =18 years);

• have received IV alteplase for AIS according to standard criteria;

• have a mild-moderate level of neurological impairment (e.g. score <10 on the NIHSS);

• stable and without any critical care needs at the end of the infusion of alteplase.

Exclusion Criteria:

• major neurological impairment;

• definite clinical contraindication or indication to either low-intensity or standard neurological monitoring.

Related Conditions & MeSH terms

• Acute Ischemic Stroke Patients Receiving Reperfusion Therapy
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Other:
• Low-intensity monitoring strategy
Post-tpa patients will be monitored in a lower intensity with less vital status and neurological assessment
• Guideline recommended standard monitoring
Post-tpa patients will be monitored in the usual care monitoring environment

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Canberra Hospital	Canberra	Australian Capital Territory
Australia	Concord Hospital	Concord	New South Wales
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	St George Public Hospital	Kogarah	New South Wales
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Royal North Shore Hospital	Sydney	New South Wales
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Chile	Hospital Base de Osorno	Osorno
Chile	Hospital de Puerto Montt	Puerto Montt	Los Lagos
Chile	Clinica Alemana de Santiago	Santiago	Región Metropolitana
Chile	Hospital del Pino	Santiago	Región Metropolitana
Chile	Hospital La Florida Dra. Eloisa Díaz	Santiago	Región Metropolitana
Chile	Hospital Padre Hurtado	Santiago	Región Metropolitana
Chile	Hospital Sótero del Rio	Santiago	Región Metropolitana
Chile	Hospital Carlos Van Buren	Valparaíso
China	Shenyang First People's Hospital	Shenyang
Malaysia	Hospital Universiti Sains Malaysia	Kota Bharu
Malaysia	Universiti Kebangssan Malaysia Medical Center	Kuala Lumpur
Malaysia	Hospital Pengajar Universiti Putra Malaysia (Hpupm)	Serdang
Mexico	Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez	Ciudad de Mexico
Mexico	Hospital Regional ISSSTE de Puebla	Puebla
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Countess of Chester Hospital	Chester
United Kingdom	Royal Devon and Exeter Hospital	Exeter
United Kingdom	Kings College Hospital	London
United Kingdom	Leicester Royal Infirmary	London
United Kingdom	St George's University Hospitals	London
United Kingdom	University College London Hospitals	London
United Kingdom	Luton and Dunstable University Hospital	Luton
United Kingdom	Nottingham University Hospitals	Nottingham
United Kingdom	Warnford Hospital	Oxford
United Kingdom	Peterborough City Hospital	Peterborough
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	ThedaCare Regional Medical Center Appleton	Appleton	Wisconsin
United States	The John Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	SSM Health DePaul Hospital	Bridgeton	Missouri
United States	Howard County General Hospital	Columbia	Maryland
United States	OhioHealth Research Institute - Riverside Methodist Hospital	Columbus	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Cone Health	Greensboro	North Carolina
United States	Penn State Health	Hershey	Pennsylvania
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Centura St. Anthony Hospital	Lakewood	Colorado
United States	Centura Littleton Adventist Hospital	Littleton	Colorado
United States	Ascension Providence Hospital	Novi	Michigan
United States	INTEGRIS Southwest Medical Center	Oklahoma City	Oklahoma
United States	Renown Health	Reno	Nevada
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Massachusetts Worcester	Worcester	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Craig Anderson	Genentech, Inc., Johns Hopkins University, The George Institute for Global Health, Australia

Countries where clinical trial is conducted

United States,  Australia,  Chile,  China,  Malaysia,  Mexico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	modified Rankin scale (mRS); shift analysis across full range of scores	Physical function measured according to a 7 level categorical scale, where 0-1 indicates no or minimal symptoms, 2-5 indicates increasing levels of disability/dependencey, and 6=death	day 90
Secondary	frequency of major Symptomatic intracerebral hemorrhage	intracerebral hemorrhage on brain imaging associated with significant neurological deterioration or death over 24 hours	day 90
Secondary	Measures of hospital costs	to allow economic analysis of treatment interventions at a country level	day 90
Secondary	any serious adverse event during follow-up		Within 90 days