Clinical Surveillance vs. Anticoagulation for Low-risk Patients with Isolated Subsegmental Pulmonary Embolism: A Multicenter Randomized Placebo-Controlled Non-Inferiority Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Insel Gruppe AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

22 Apr 2026 → ongoing

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Swiss National Foundation · Bayer AG

External identifiers

EU CT number

2023-507801-32-00

EudraCT number

2020-000353-26

ClinicalTrials.gov

NCT04263038

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The overall objective of this trial will be to evaluate the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with isolated SSPE.
Objective 1: To compare the frequency of symptomatic, recurrent venous thromboembolism (VTE) in low-risk patients with isolated SSPE randomized to receive clinical surveillance or anticoagulation.

Secondary objectives 2

1. Objective 2: To compare the frequency of clinically significant bleeding and all-cause mortality in low-risk patients with isolated SSPE randomized to receive clinical surveillance or anticoagulation.
2. Objective 3: To compare health-related quality of life, functional status, and medical resource utilization in low-risk patients with isolated SSPE randomized to receive clinical surveillance or anticoagulation.

Conditions and MedDRA coding

Isolated Subsegmental Pulmonary Embolism

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Informed Consent as documented by signature
2. Age ≥18 years
3. Objective diagnosis of symptomatic or asymptomatic isolated SSPE
4. Affiliation to the general health insurance regime (only for study sites in France)

Exclusion criteria 16

1. Presence of leg DVT or upper extremity DVT (subclavian vein or above)
2. Active cancer, defined as cancer treated with surgery, chemotherapy, radiotherapy, or palliative care during the last 6 months; or presence of metastatic cancer
3. ≥1 prior episode of unprovoked VTE (absence of a transient or permanent risk factor)
4. Clinical instability (systolic blood pressure <100 mm Hg or arterial oxygen saturation <92% at ambient air) at the time of presentation
5. Active bleeding or at high risk of bleeding
6. Severe renal failure (creatinine clearance <30ml/min)
7. Severe liver insufficiency (Child-Pugh B or C)
8. Concomitant use of strong CYP3A4 inhibitors or strong CYP3A4 inducers
9. Known hypersensitivity to rivaroxaban
10. Need for therapeutic anticoagulation for another reason
11. Therapeutic anticoagulation for >72 hours for any reason at the time of screening
12. Hospitalized for >72 hours prior to the diagnosis of isolated SSPE (hospital-acquired VTE)
13. Known pregnancy or breast feeding (pregnancy test to be performed for women of childbearing potential)
14. Lack of safe contraception in women of childbearing potential
15. Refusal or inability to provide informed consent (specification for study sites in France: guardianship, conservatorship, judicial protection or unprotected person with a cognitive impairment that does not allow sufficient understanding of the study procedures)
16. Prior enrolment in this trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome will be the proportion of recurrent, clinically symptomatic, objectively confirmed VTE within 90 days of randomization, defined as recurrent fatal or nonfatal pulmonary embolism (PE) or lower limb deep vein thrombosis (DVT; efficacy).

Secondary endpoints 2

1. The secondary outcomes will be the proportion of clinically significant bleeding and all-cause mortality at 90 days of randomization (safety).
2. The ancillary outcomes will be health-related quality of life, functional status, and medical resource utilization at 90 days of randomization.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Insel Gruppe AG

Sponsor organisation

Insel Gruppe AG

Address

Freiburgstrasse 18

City

Bern

Postcode

3010

Country

Switzerland

Scientific contact point

Organisation

Insel Gruppe AG

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Insel Gruppe AG

Contact name

Clinical Trial Information Desk

Locations

3 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 3 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications