Discovery of New Cancer in the 1-year Follow-up After Ischemic Stroke in Patients at Risk: The INVISIBLE-1 Study

Sponsor

Insel Gruppe AG, University Hospital Bern (Other)

Overall Status

Recruiting

CT.gov ID

NCT06100718

Collaborator

(none)

370

Enrollment

Locations

Anticipated Duration (Months)

123.3

Patients Per Site

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

INVISIBLE-1 aims to prospectively follow patients up to one year after ischemic stroke to:

Determine the cumulative incidence of occult cancer in patients with embolic stroke of undetermined source (ESUS) and elevated D-dimer
Describe occult cancer characteristics and spontaneous course of occult cancer

Methodology

The investigators will include 370 stroke patients with elevated D-dimer (≥ 820 μg/L) at the time of stroke, suspicion of ESUS after initial workup and without known cancer. The investigators will perform a follow-up telephone interview at one year to assess the occurrence of a new cancer and characterize the course of the disease.

Significance

Determining the real incidence of occult cancer in high-risk patients will help support the implementation of screening trials in the future. Faster detection and treatment of occult cancers would significantly impact patient' outcomes by offering faster cancer treatment and optimal secondary stroke prevention.

Condition or Disease	Intervention/Treatment	Phase
Cancer-related Stroke Paraneoplastic Coagulopathy Occult Cancer Ischemic Stroke Embolic Stroke of Undetermined Source D-dimer

Detailed Description

INVISIBLE-1 is the first prospective study conducting a 1-year post-stroke follow-up telephone interview in preselected stroke patients at high-risk for occult cancer.

INVISIBLE-1 aims to:

Prospectively determine the cumulative incidence of occult cancer in patients with elevated D-dimer and ESUS within 1 year after the ischemic stroke
Describe occult cancer characteristics and spontaneous course of occult cancer

Hypothesis

Elevated D-dimer and suspicion of ESUS at admission may predict an underlying unknown cancer at the time of index stroke. The investigators hypothesize that the cumulative incidence of newly diagnosed cancer within 1 year after stroke reaches 15% in patients presenting these characteristics. This percentage is higher than the 10% currently known according to available retrospective studies.

Project design

To ensure the recruitment of the majority of potential occult cancer patients, the investigators set the D-dimer cut-off for inclusion of ≥ 820 μg/L at admission, based on our intern retrospective analyses of 1001 patients (OCCULT-5 score). In patients with ESUS, this cut-off was associated with a sensitivity of 91% and a specificity of 56% for the presence of an occult cancer diagnosed within 1 year after the index-stroke.

As suggested by the current evidence, the investigators decided to set the limit for diagnosis of new cancer at 1 year after the index stroke. Beyond this period, the causality is questionable in our opinion.

Study Design

Study Type:

Observational

Anticipated Enrollment :

370 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Discovery of New Cancer in the 1-year Follow-up After Ischemic Stroke in Patients at Risk: The INVISIBLE-1 Study

Actual Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Study group Acute ischemic stroke patients at high-risk for underlying occult cancer (elevated D-dimer and suspicion of ESUS at admission)

Outcome Measures

Primary Outcome Measures

Number of participants with newly diagnosed cancer (occult cancer) [Within 1 year after ischemic stroke]

Secondary Outcome Measures

Determination of occult cancer characteristics [Within 1 year after ischemic stroke]
The description of the specific characteristics of occult cancers is defined by the location of the cancer, the histological type of cancer, the date of suspicion of cancer (e.g. via imaging), the type of investigation leading to the suspicion of cancer, the date of final diagnosis via histology, the presence of metastases at diagnosis, the type of treatment provided and the date of start of treatment.
Long-term functional outcome using the modified Rankin Scale (mRS) in stroke patients with occult cancer [At 1 year after ischemic stroke]
The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The higher the mRS score, the more disabled or dependent the patient (mRS 6 represents death).
All-cause mortality rate and cause-specific mortality rate [At 1 year after ischemic stroke]
Rate of recurrent ischemic stroke, or systemic embolism in occult cancer-related stroke [Within 1 year after ischemic stroke]
Stroke severity assessed with the National Institutes of Health Stroke Scale (NIHSS) in patients with occult cancer [Baseline]
NIHSS is used to quantify stroke severity. It ranges from 0 to a maximum of 42 points. The higher the score, the more extensive the stroke.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Inclusion Criteria:

Informed consent as documented by signature from patient or next of kin
Age ≥ 18 years old
Acute ischemic stroke with symptom onset within 48 h before admission
Acute ischemic stroke with:
persistent signs and symptoms of stroke lasting for ≥ 24 hours OR
acute brain infarction documented by computer tomography (CT) or MRI
D-dimer ≥ 820 μg/L measured after symptom-onset and within 24h after admission
Embolic stroke of unknown source (ESUS)* after initial work-up (acute cerebral imaging, 12-lead electrocardiogram, cardiac monitoring for at least 24h and echocardiography)

Exclusion Criteria:

Active cancer** known at time of index-stroke
Intravenous Thrombolysis administrated prior to D-dimer measurement: Use of external laboratory value possible if available
New diagnosis of central nervous system cancer
Patient or next of kin (in case of lacking capacity) unlikely to be compliant or available for study follow-up interview

ESUS*: According to the definition from the NAVIGATE ESUS randomized trial: Non-lacunar ischemic stroke occurring in a patient in whom investigations did not show another specifically treatable underlying stroke etiology, primarily >50% stenosis in a proximal extracranial or intracranial artery, atrial fibrillation, other major-risk cardioembolic sources, or other determined etiology.

Active Cancer**: According to the definition from the International Society on Thrombosis and Haemostasis: Cancer diagnosed within the previous six months, recurrent, regionally advanced or metastatic cancer, cancer for which treatment had been administered within six months, or hematological malignancy that is not in complete remission for more than 5 years.

► Patients with history of cancer not meeting these criteria anymore can be included in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dept. of Neurology, Centre Hospital Universitaire Vaudois	Lausanne	Vaud	Switzerland	1011
2	Dept. of Neurology, Universitätsspital Basel	Basel		Switzerland	4031
3	Dept, of Neurology, Inselspital, University of Bern	Bern		Switzerland	3010