Optimal Post Tpa-Iv Monitoring in Ischemic Stroke

NCT ID: NCT03734640

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 4922 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-28
• Study Completion Date: 2025-01-23

Brief 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.

Detailed 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.

Conditions

Acute Ischemic Stroke Patients Receiving Reperfusion Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: SINGLE

Study Groups

Guideline recommended standard monitoring

vital signs (HR, BP) and neurological assessment (GCS and NIHSS) 15-30mins x 2 hours, 30mins x 6 hours, 1hourly x 16 hours in usual care monitoring environment

Group Type: PLACEBO_COMPARATOR

Guideline recommended standard monitoring

Intervention Type: OTHER

Post-tpa patients will be monitored in the usual care monitoring environment

Low-intensity monitoring strategy

vital signs (HR, BP) and neurological assessment (GCS and/or NIHSS) 15-30mins x 2 hours, 2hourly x 8 hours, 4hourly x 14 hours in a non-ICU ward

Group Type: ACTIVE_COMPARATOR

Low-intensity monitoring strategy

Intervention Type: OTHER

Post-tpa patients will be monitored in a lower intensity with less vital status and neurological assessment

Interventions

Low-intensity monitoring strategy

Post-tpa patients will be monitored in a lower intensity with less vital status and neurological assessment

Intervention Type: OTHER

Guideline recommended standard monitoring

Post-tpa patients will be monitored in the usual care monitoring environment

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

The George Institute for Global Health, Australia

OTHER

Sponsor Role: collaborator

Craig Anderson

OTHER

Sponsor Role: lead

Responsible Party

Craig Anderson

Executive Director

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Craig S Anderson, MD PhD

Role: PRINCIPAL_INVESTIGATOR

The George Institute

Victor C Urrutia, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Centura St. Anthony Hospital

Lakewood, Colorado, United States

Centura Littleton Adventist Hospital

Littleton, Colorado, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

The John Hopkins Hospital

Baltimore, Maryland, United States

Howard County General Hospital

Columbia, Maryland, United States

University of Massachusetts Worcester

Worcester, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Ascension Providence Hospital

Novi, Michigan, United States

SSM Health DePaul Hospital

Bridgeton, Missouri, United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Research Medical Center

Kansas City, Missouri, United States

Renown Health

Reno, Nevada, United States

University of Rochester Medical Center

Rochester, New York, United States

Cone Health

Greensboro, North Carolina, United States

OhioHealth Research Institute - Riverside Methodist Hospital

Columbus, Ohio, United States

INTEGRIS Southwest Medical Center

Oklahoma City, Oklahoma, United States

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Penn State Health

Hershey, Pennsylvania, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

ThedaCare Regional Medical Center Appleton

Appleton, Wisconsin, United States

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

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, Australia

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Hospital de Puerto Montt

Port Montt, Los Lagos Region, Chile

Clinica Alemana de Santiago

Santiago, Santiago Metropolitan, Chile

Hospital del Pino

Santiago, Santiago Metropolitan, Chile

Hospital La Florida Dra. Eloisa Díaz

Santiago, Santiago Metropolitan, Chile

Hospital Padre Hurtado

Santiago, Santiago Metropolitan, Chile

Hospital Sótero del Rio

Santiago, Santiago Metropolitan, Chile

Hospital Base de Osorno

Osorno, , Chile

Hospital Carlos Van Buren

Valparaíso, , Chile

Shenyang First People's Hospital

Shenyang, , China

Hospital Universiti Sains Malaysia

Kota Bharu, , Malaysia

Universiti Kebangssan Malaysia Medical Center

Kuala Lumpur, , Malaysia

Hospital Pengajar Universiti Putra Malaysia (Hpupm)

Serdang, , Malaysia

Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez

Mexico City, , Mexico

Hospital Regional ISSSTE de Puebla

Puebla City, , Mexico

Addenbrookes Hospital

Cambridge, , United Kingdom

Countess of Chester Hospital

Chester, , United Kingdom

Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Leicester Royal Infirmary

London, , United Kingdom

University College London Hospitals

London, , United Kingdom

Kings College Hospital

London, , United Kingdom

St George's University 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 Kingdom

Countries

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

References

Anderson CS, Summers D, Ouyang M, Sui Y, Johnson B, Billot L, Malavera A, Faigle R, Munoz-Venturelli P, Day D, Liu X, Li Q, Song L, Robinson TG, Gonzalez F, Urrutia-Goldsack F, Iacobelli M, Montalbano M, Pruski A, Delcourt C, Durham AC, Ebraimo A, Van Ta HH, Ghosh P, Leonhardt-Caprio A, Nguyen HT, Ton MD, Jan S, Liu H, Lindley RI, Arauz A, Mercado A, Zaidi WAW, Khatri P, Wang X, Urrutia VC; OPTIMISTmain Investigators. Safety and efficacy of low-intensity versus standard monitoring following intravenous thrombolytic treatment in patients with acute ischaemic stroke (OPTIMISTmain): an international, pragmatic, stepped-wedge, cluster-randomised, controlled non-inferiority trial. Lancet. 2025 May 31;405(10493):1909-1922. doi: 10.1016/S0140-6736(25)00549-5. Epub 2025 May 21.

Reference Type: DERIVED

PMID: 40412428 (View on PubMed)

Other Identifiers

OPTIMISTmain

Identifier Type: -

Identifier Source: org_study_id