Catheter-directed thrombolysis in intermediate-high risk acute pulmonary embolism

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fakultni Nemocnice Kralovske Vinohrady

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2024-10-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516144-25-00

EudraCT number

2022-002218-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To investigate clinical outcomes (combined endpoint, clinical composite of any of following – any death, PE recurrence, cardiorespiratory decompensation) in patients treated by CDT compared to standard anticoagulation therapy.

Secondary objectives 6

1. To investigate efficacy of CDT compared to standard anticoagulation.
2. To investigate adverse events including major and minor bleeding complications.
3. To evaluate duration of intensive care unit (coronary care unit) length of stay and hospital length of stay.
4. To evaluate hospitalization cost (cost-effectiveness).
5. To evaluate patients´ functional status, performance and quality of life.
6. To evaluate the incidence of chronic thromboembolic pulmonary hypertension (CTEPH).

Conditions and MedDRA coding

intermediate-high risk acute pulmonary embolism

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age > 18 years and  80 years.
2. Computed tomography angiography (CTA)-verified proximal PE AND symptom onset < 14 days prior.
3. Intermediate-high risk PE with a sPESI score ≥ 1 AND RV dysfunction AND an elevated biomarker (hs-troponin or NT-proBNP) level.
4. Signed informed consent

Exclusion criteria 10

1. Active clinically significant bleeding.
2. Any haemorrhagic stroke OR a recent (< 6 months) ischaemic stroke/transient ischaemic attack.
3. Recent (< 3 months) cranial trauma OR another active intracranial/intraspinal process.
4. Major surgery within 7 days prior.
5. Active malignancy OR other severe illness with expected survival < 2 years.
6. Haemoglobin level < 80 g/L; international normalised ratio > 2.0, platelet count ≤ 100 x 109; creatinine level > 200 μmol/L.
7. Pregnant or breastfeeding, fertility without previous exclusion of gravidity.
8. Allergic to thrombolytics or heparin or low-molecular-weight heparin (LMWH), contrast allergy, a history of heparin-induced thrombocytopenia.
9. Floating thrombi in transit through a patent foramen ovale.
10. Participation in another clinical trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. All-cause mortality – [ Time Frame: Within 7 days of randomization ]
2. PE recurrence (non-fatal symptomatic and objectively confirmed recurrence of PE by repeated CTA) – [ Time Frame: Within 7 days of randomization ]
3. Cardiorespiratory decompensation or collapse* – [ Time Frame: Within 7 days of randomization ]

Secondary endpoints 15

1. All individual components of primary endpoint – [ Time Frame: Within 7 days, 30 days, and 12 months ]
2. First-line therapy failure** – [ Time Frame: Hospitalization ]
3. Ischemic or haemorrhagic stroke [ Time Frame: Within 7 days and 30 days ]
4. Serious adverse events – [ Time Frame: Within 12 months ]
5. Duration of hospitalization for the index acute PE event (Time from admission to discharge from hospital) – [ Time Frame: Within 30 days ]
6. Duration of stay at the intensive, intermediate or coronary care unit during hospitalization for the index acute PE event (Time from admission to discharge from ICU, intermediate, or CCU) – [ Time Frame: Within 30 days ]
7. Hospitalization cost (cost-effectiveness analysis) – [ Time Frame: Within 30 days ]
8. GUSTO major (moderate and severe) bleeding*** – [ Time Frame: Within 30 days ]
9. International Society on Thrombosis and Hemostasis (ISTH) major bleeding**** – [ Time Frame: Within 30 days ]
10. All bleeding complications scored by the Bleeding Academic Research Consortium (BARC) classification – [ Time Frame: Within 30 days and 12 months ]
11. Change in the RV-to-LV diameter ratio, systolic pulmonary artery pressure (sPAP), Tricuspid annular plane systolic excursion (TAPSE), Tissue Doppler imaging-derived Tricuspid lateral annular Systolic Velocity (S´ TDI) as measured by echocardiography – [ Time Frame: Between Randomization and 24±3 hours, at 30 days, 12 months and 24 months ]
12. Functional status as measured by World Health Organization (WHO) functional class***** – [ Time Frame: Discharge, 30 days, 12 months and 24 months ]
13. Functional status as measured by 6-Minute Walk Test (6MWT) ****** – [ Time Frame: 12 months and 24 months ]
14. Quality of life using EQ-5D scale******* – [ Time Frame: 30 days, 12 months and 24 months ]
15. Diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) – [ Time Frame: Within 24 months ]

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fakultni Nemocnice Kralovske Vinohrady

Sponsor organisation

Fakultni Nemocnice Kralovske Vinohrady

Address

Srobarova 1150/50, Vinohrady Vinohrady

City

Prague

Postcode

100 00

Country

Czechia

Scientific contact point

Organisation

Fakultni Nemocnice Kralovske Vinohrady

Contact name

MUDr. Josef Kroupa

Public contact point

Organisation

Fakultni Nemocnice Kralovske Vinohrady

Contact name

MUDr. Josef Kroupa

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Results and documents

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

Documents 15 files

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

Application history

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