Clinical trial NCT03734640: Optimal Post Tpa-Iv Monitoring in Ischemic Stroke
Official title: Optimal Post Tpa-Iv Monitoring in Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Ischemic Stroke Patients Receiving Reperfusion Therapy
Lead sponsor: The George Institute for Global Health, China
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Johns Hopkins University
name: The George Institute for Global Health, Australia
First posted: 2018-11-08
Enrollment: 4922
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: stepped wedge cluster randomized
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: modified Rankin scale (mRS); shift analysis across full range of scores
timeFrame: day 90
Secondary outcomes:
measure: frequency of major Symptomatic intracerebral hemorrhage
timeFrame: day 90
measure: Measures of hospital costs
timeFrame: day 90
measure: any serious adverse event during follow-up
timeFrame: Within 90 days
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: Centura St. Anthony Hospital
state: Colorado
city: Littleton
country: United States
facility: Centura Littleton Adventist Hospital
state: Colorado
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: The John Hopkins Hospital
state: Maryland
city: Columbia
country: United States
facility: Howard County General Hospital
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Worcester
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Novi
country: United States
facility: Ascension Providence Hospital
state: Michigan
city: Bridgeton
country: United States
facility: SSM Health DePaul Hospital
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Reno
country: United States
facility: Renown Health
state: Nevada
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Greensboro
country: United States
facility: Cone Health
state: North Carolina
city: Columbus
country: United States
facility: OhioHealth Research Institute - Riverside Methodist Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Southwest Medical Center
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Health
state: Pennsylvania
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Appleton
country: United States
facility: ThedaCare Regional Medical Center Appleton
state: Wisconsin
city: Canberra
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Concord
country: Australia
facility: Concord Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Public Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Puerto Montt
country: Chile
facility: Hospital de Puerto Montt
state: Los Lagos
city: Santiago
country: Chile
facility: Clinica Alemana de Santiago
state: Región Metropolitana
city: Santiago
country: Chile
facility: Hospital del Pino
state: Región Metropolitana
city: Santiago
country: Chile
facility: Hospital La Florida Dra. Eloisa Díaz
state: Región Metropolitana
city: Santiago
country: Chile
facility: Hospital Padre Hurtado
state: Región Metropolitana
city: Santiago
country: Chile
facility: Hospital Sótero del Rio
state: Región Metropolitana
city: Osorno
country: Chile
facility: Hospital Base de Osorno
city: Valparaíso
country: Chile
facility: Hospital Carlos Van Buren
city: Shenyang
country: China
facility: Shenyang First People's Hospital
city: Kota Bharu
country: Malaysia
facility: Hospital Universiti Sains Malaysia
city: Kuala Lumpur
country: Malaysia
facility: Universiti Kebangssan Malaysia Medical Center
city: Serdang
country: Malaysia
facility: Hospital Pengajar Universiti Putra Malaysia (Hpupm)
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez
city: Puebla
country: Mexico
facility: Hospital Regional ISSSTE de Puebla
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: London
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: University College London Hospitals
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: St George's University Hospitals
city: Luton
country: United Kingdom
facility: Luton and Dunstable University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
city: Oxford
country: United Kingdom
facility: Warnford Hospital
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
Study officials:
affiliation: The George Institute
name: Craig S Anderson, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Victor C Urrutia, MD
role: PRINCIPAL_INVESTIGATOR
References: