Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Authorised, recruitment pending
Participants planned
84
Countries
1
Sites
2
Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
To evaluate the safety and efficacy of DOAC versus VKA in CTEPH/CTED patients receiving BPA, based on the composite endpoint of periprocedural bleeding (life- threatening or disabling bleeding, vascular injury or access site complications) and lung injury within 24 hours after BPA on a per-session basis.
Key facts
- Sponsor
- St. Antonius Ziekenhuis
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]
- Decision date (initial)
- 2024-11-15
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-518803-23-00
- EudraCT number
- 2020-004888-29
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To evaluate the safety and efficacy of DOAC versus VKA in CTEPH/CTED patients receiving BPA, based on the composite endpoint of periprocedural bleeding (life- threatening or disabling bleeding, vascular injury or access site complications) and lung injury within 24 hours after BPA on a per-session basis.
Secondary objectives 3
- To evaluate long-term safety of anticoagulant medicine in CTEPH/CTED patients receiving BPA on a per-patient basis.
- To evaluate long-term efficacy of anticoagulant medicine and quality of life (QoL) in CTEPH/CTED patients receiving BPA on a per-patient basis.
- To evaluate the coagulation potency of DOAC versus VKA in CTEPH/CTED patients receiving BPA (sub-study).
Conditions and MedDRA coding
Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Established CTEPH or CTED diagnosis according to the guideline, with at least 3 months of anticoagulation treatment.
- Inoperable patients, patients reluctant to undergo surgery or patients with residual PH after PEA and accepted for BPA treatment.
- Accessible thromboembolic lesions for BPA.
Exclusion criteria 5
- Operable CTEPH or CTED patients accepted for PEA.
- Contra-indications for BPA: right-sided mechanical heart valve, thrombus or myxoma in the right atrium or right-sided valvular endocarditis.
- Contra-indications for DOAC treatment: e.g. mechanical heart valves, myocardial thrombus, triple positive antiphospholipid syndrome, morbid obesity and (status after) bariatric treatment or major gastrointestinal resections and combination with CYP3A4 inhibitors and inductors. Anticoagulation dosage should be adjusted depending on renal function and drug interaction.
- High risk patients for bleeding complications: previous life-threatening bleeding (e.g. intracranial bleeding), age >80 years or pulmonary vascular resistance > 10 woods units (WU).
- Life-expectancy <1 year.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Combination of periprocedural bleeding (life-threatening or disabling bleeding, vascular injury or access site problems) based on the international criteria (PH-symposium, VARC and BARC [2-3 and 5]) or lung injury (radiographic opacity with/without haemoptysis, with/without hypoxaemia) within 24 hours after BPA, on a per-session basis.
Secondary endpoints 6
- Individual items of the combined primary endpoint (on a per-session basis).
- Procedure related endpoints (on a per-session basis): 1) Allergic reaction to contrast (assessed for total complication rate, not for VKA vs DOAC). 2) Renal dysfunction
- Venous thromboembolism.
- Long-term bleeding complications based on international criteria.
- All-cause mortality.
- Non-scheduled hospitalization.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 6
Eliquis 2.5 mg film-coated tablets
PRD1722226 · Product
- Active substance
- Apixaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 4500 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF02 — -
- Marketing authorisation
- EU/1/11/691/015
- MA holder
- BRISTOL-MYERS SQUIBB/PFIZER EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Lixiana 15 mg film-coated tablets
PRD2965631 · Product
- Active substance
- Edoxaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 54000 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF03 — -
- Marketing authorisation
- EU/1/15/993/001
- MA holder
- DAIICHI SANKYO EUROPE GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Lixiana 30 mg film-coated tablets
PRD2965666 · Product
- Active substance
- Edoxaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 54000 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF03 — -
- Marketing authorisation
- EU/1/15/993/002
- MA holder
- DAIICHI SANKYO EUROPE GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Lixiana 60 mg film-coated tablets
PRD2965685 · Product
- Active substance
- Edoxaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- OTHER USE
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 54000 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF03 — -
- Marketing authorisation
- EU/1/15/993/003
- MA holder
- DAIICHI SANKYO EUROPE GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD1946591 · Product
- Active substance
- Dabigatran Etexilate
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 150 mg milligram(s)
- Max total dose
- 135000 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AE07 — -
- Marketing authorisation
- EU/1/08/442/017
- MA holder
- BOEHRINGER INGELHEIM INTERNATIONAL GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Xarelto 2.5 mg film-coated tablets
PRD1775240 · Product
- Active substance
- Rivaroxaban
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 18000 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF01 — -
- Marketing authorisation
- EU/1/08/472/035
- MA holder
- BAYER AG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 2
Acenocoumarol CF 1 mg, tabletten
PRD386090 · Product
- Active substance
- Acenocoumarol
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 1 mg milligram(s)
- Max total dose
- 900 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AA07 — ACENOCOUMAROL
- Marketing authorisation
- RVG 50674
- MA holder
- CENTRAFARM B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fenprocoumon Sandoz 3 mg, tabletten
PRD744706 · Product
- Active substance
- Phenprocoumon
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 3 mg milligram(s)
- Max total dose
- 2700 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AA04 — PHENPROCOUMON
- Marketing authorisation
- RVG 21068
- MA holder
- SANDOZ B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
St. Antonius Ziekenhuis
2
Total trials
Academic / Non-commercial
- Sponsor organisation
- St. Antonius Ziekenhuis
- Address
- Koekoekslaan 1
- City
- Nieuwegein
- Postcode
- 3435 CM
- Country
- Netherlands
Scientific contact point
- Organisation
- St. Antonius Ziekenhuis
- Contact name
- K. Mantzios
Public contact point
- Organisation
- St. Antonius Ziekenhuis
- Contact name
- K. Mantzios
Locations
1 EU/EEA country · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Authorised, recruitment pending | 84 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
Amsterdam UMC Stichting
Pulmonary Medicine, De Boelelaan 1117, 1081 HV, Amsterdam
St. Antonius Ziekenhuis
Cardiology, Koekoekslaan 1, 3435 CM, Nieuwegein
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-518803-23-00 | 4.3 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 4.1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Acenocoumarol | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Eliquis | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Fenprocoumon | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Lixiana | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Pradaxa | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Xarelto | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-11 | Netherlands | Acceptable 2024-11-15
|
2024-11-15 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-12-03 | Netherlands | Acceptable 2024-11-15
|
2024-12-03 |