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

Study Purpose

INVISIBLE-1 aims to prospectively follow patients up to one year after ischemic stroke to: 1. Determine the cumulative incidence of occult cancer in patients with embolic stroke of undetermined source (ESUS) and elevated D-dimer. 2. 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Unknown
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06100718
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Insel Gruppe AG, University Hospital Bern
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Simon Jung, MD
Principal Investigator Affiliation	Inselspital, University of Bern
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Switzerland
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Cancer-related Stroke, Paraneoplastic Coagulopathy, Occult Cancer, Ischemic Stroke, Embolic Stroke of Undetermined Source, D-dimer

Additional Details

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: 1. Prospectively determine the cumulative incidence of occult cancer in patients with elevated D-dimer and ESUS within 1 year after the ischemic stroke. 2. 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.

Arms & Interventions

Arms

: Study group

Acute ischemic stroke patients at high-risk for underlying occult cancer (elevated D-dimer and suspicion of ESUS at admission)

Interventions

Contact a Trial Team

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International Sites

Lausanne, Vaud, Switzerland

Status

Recruiting

Address

Dept. of Neurology, Centre Hospital Universitaire Vaudois

Lausanne, Vaud, 1011

Site Contact

Michel Patrik

[email protected]

+41 79 556 8416

Basel, Switzerland

Status

Recruiting

Address

Dept. of Neurology, Universitätsspital Basel

Basel, , 4031

Site Contact

Mira Katan, MD

[email protected]

+41 61 328 45 06

Bern, Switzerland

Status

Recruiting

Address

Dept, of Neurology, Inselspital, University of Bern

Bern, , 3010

Site Contact

Simon Jung, MD

[email protected]

+41 31 63 2 43 27

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