Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
2,625
Countries
6
Sites
21
Treatment with a Vitamin K Antagonist due to having a mechanical bileaflet aortic valve replacement.
Evaluate the safety and efficacy of a common, lower INR range in patients with bileaflet aortic mechanical valves.
Key facts
- Sponsor
- Hamilton Health Sciences Corporation
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 19 Oct 2021 → ongoing
- Decision date (initial)
- 2023-11-24
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Canadian Institutes of Health Research
External identifiers
- EU CT number
- 2023-508532-56-00
- EudraCT number
- 2019-004975-37
- ClinicalTrials.gov
- NCT03636295
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
Evaluate the safety and efficacy of a common, lower INR range in patients with bileaflet aortic mechanical valves.
Conditions and MedDRA coding
Treatment with a Vitamin K Antagonist due to having a mechanical bileaflet aortic valve replacement.
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10002916 | Aortic valve replacement | 100000004865 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Low INR to Minimize bleeding with mechanical valves Trial (LIMIT) A prospective, randomized, open-label, blinded end-point (PROBE), multicenter clinical trial. The intervention of interest is a low INR target range (1.5 to 2.5) compared to the current practice as per guideline recommendations.
|
Randomised Controlled | None | Intervention Group - INR Target Range 1.5-2.5: The intervention group will receive a dose titrated to achieve an INR target of 1.5-2.5. Control Group - Guideline Recommended INR Target Range: The control group will receive a dose titrated to achieve the current guideline-recommended INR range. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Have had a bileaflet mechanical heart valve implant in the aortic position at least 3 months ago (greater than or equal to 3 months)
- Be at least 18 years of age at the time of enrollment (greater than or equal to 18 years of age)
- Provide written informed consent (either from the patient or substitute decision-maker)
Exclusion criteria 3
- Have a second implanted mechanical valve (any position)
- Lower boundary of planned INR range is less than 2.0
- Pregnant or expecting to become pregnant during the study follow-up
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Thrombosis/thromboembolism (composite of ischemic stroke, systemic thromboembolism, valve thrombosis) and major bleeding.
Secondary endpoints 14
- All-cause mortality (selected rather than cardiovascular mortality, as cause-specific mortality is often difficult to ascertain or define in complex cardiovascular patients in whom multi-end-organ dysfunction may accompany cardiovascular decline)
- All clinically important bleeding
- Minor bleeding
- All stroke
- Ischemic stroke
- Hemorrhagic stroke
- Type 1, 2 or 3 myocardial infarction
- Systemic thromboembolism
- Valve thrombosis
- Pulmonary embolism
- Deep vein thrombosis
- New renal replacement therapy
- Time in therapeutic range
- Proportion of patients with extreme INR values (>4)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 5
SUB00090MIG · Substance
- Active substance
- Warfarin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00090MIG · Substance
- Active substance
- Warfarin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05211MIG · Substance
- Active substance
- Acenocoumarol
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 4 mg milligram(s)
- Max total dose
- 4 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00090MIG · Substance
- Active substance
- Warfarin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09781MIG · Substance
- Active substance
- Phenprocoumon
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 12 mg milligram(s)
- Max total dose
- 12 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 5
SUB09781MIG · Substance
- Active substance
- Phenprocoumon
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 12 mg milligram(s)
- Max total dose
- 12 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05211MIG · Substance
- Active substance
- Acenocoumarol
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 4 mg milligram(s)
- Max total dose
- 4 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00090MIG · Substance
- Active substance
- Warfarin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00090MIG · Substance
- Active substance
- Warfarin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00090MIG · Substance
- Active substance
- Warfarin
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Hamilton Health Sciences Corporation
- Sponsor organisation
- Hamilton Health Sciences Corporation
- Address
- 100 King Street West
- City
- Hamilton
- Postcode
- L8P 1A2
- Country
- Canada
Scientific contact point
- Organisation
- Hamilton Health Sciences Corporation
- Contact name
- Dr. Emilie Belley-Cote
Public contact point
- Organisation
- Hamilton Health Sciences Corporation
- Contact name
- Dr. Emilie Belley-Cote
Locations
6 EU/EEA countries · 21 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 175 | 4 |
| Denmark | Ongoing, recruiting | 175 | 3 |
| Germany | Ongoing, recruiting | 175 | 3 |
| Italy | Ongoing, recruiting | 200 | 6 |
| Netherlands | Ongoing, recruiting | 100 | 1 |
| Spain | Ongoing, recruiting | 150 | 4 |
| Rest of world
Saudi Arabia, Australia, Korea, Republic of, Brazil, Russian Federation, Botswana, Canada, South Africa, Pakistan, Cameroon, United Kingdom, Chile
|
— | 1,650 | — |
Investigational sites
Algemeen Ziekenhuis Damiaan Oostende
Cardiology, Gouwelozestraat 100, 8400, Ostend
UZ Leuven
Cardiale Heelkunde, Herestraat 49, 3000, Leuven
Ziekenhuis Oost Limburg
Cardiology, Synaps Park 1, 3600, Genk
Imelda
Cardiac Surgery, Imeldalaan 9, 2820, Bonheiden
Esbjerg Og Grindsted Sygehus
Cardiology, Finsensgade 35, 6700, Esbjerg
Sygehus Soenderjylland Soenderborg
Cardiology, Kresten Philipsens Vej 15, 6200, Aabenraa
Aarhus Universitetshospital
Cardiology, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
University Of Regensburg
Cardio Thoracic Surgery, Dr.-Gessler-Strasse 17, Koenigswiesen-Dechbetten-Grosspruefening, Regensburg
Universitätsklinikum Jena
Cardiac and Thoracic Surgery, Am Klinikum 1, 07747, Jena
Justus-Liebig-Universitaet Giessen
Cardiovascular, Rudolf-Buchheim-Strasse 7, 35392, Giessen
Citta di Lecce Hospital GVM Care & Research
Cardiac Surgery, Via Prov. Per Arnesano Km 4, 73100, Lecce
Azienda Ospedaliero Universitaria Delle Marche
Cardiac Surgery, Via Conca 71, 60126, Ancona
Azienda Ospedaliero Universitaria Ospedali Riuniti
Cardiac Surgery, Viale Luigi Pinto 1, 71122, Foggia
Careggi University Hospital
Cardiovascular, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
IRCCS Policlinico San Matteo
Cardiologia 1, Viale Camillo Golgi 19, 27100, Pavia
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo
Cardiac Surgery, via Venezia, 16, Alessandria
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Cardiology, Dr. Molewaterplein 60, 3015 GJ, Rotterdam
Hospital Universitario 12 De Octubre
Cardiac Surgery, Avenida De Cordoba Sn, 28041, Madrid
Hospital Universitario La Paz
Cardiology, Paseo De La Castellana 261, 28046, Madrid
Hospital de la Santa Creu i Sant Pau
Associacion Colaboracion Cochrane Iberoamericana, c/ Sant Quinti, 77-79, Barcelona
Unidad de Ensayos Clínicos Hospital Universitario de la Princesa
Cardiac Surgery, Calle Diego de Leon 62, 28006, Madrid
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2021-10-27 | 2021-12-01 | |||
| Denmark | 2025-04-23 | 2025-07-03 | |||
| Germany | 2025-04-24 | 2025-06-16 | |||
| Italy | 2025-07-02 | 2025-07-02 | |||
| Netherlands | 2022-11-21 | 2023-12-16 | |||
| Spain | 2021-10-19 | 2021-11-04 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-96591
- Halt date
- 2025-07-22
- Planned restart
- 2025-10-01
- Member states concerned
- Italy
- Publication date
- 2025-09-04
- Reason
- Medicinal Product related
- Explanation
- AIFA communicated outside of CTIS to an external participating site and specified that the sponsor must comply with the process for distribution through community pharmacies. Communication was then escalated to the sponsor. The protocol and all submission information has indicated that patients are to be taking a Vitamin K Antagonist prior to inclusion in the trial - the intervention of interest is a low INR target range (1.5 to 2.5) compared to the current practice as per guideline recommendations.
Also specified was that SM-5 was not responded to despite the submission and authorization of SM-7. Randomization permissions turned off for sites on July 22, 2025 after one patient randomized to the trial. Patient randomized to standard of care INR arm, thereby not involving any additional risk to the patient.
Treatment stopped not applicable - patient was randomized to the standard of care arm. - Follow-up measures
- Sponsor and EU Representative/Italian National Leader have attempted to contact AIFA during the month of August. Intention is to schedule a call with the CT Unit to further discuss the communications.
- Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 157 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol Change Summary_Redacted_2023-508532-56-00 | 10-1 |
| Protocol (for publication) | D1_Protocol_Redacted_v7-9_2023-508532-56-00 | 9 |
| Protocol (for publication) | D2_Protocol_Final_Redacted_2023-508532-56-00 | 10-1 |
| Protocol (for publication) | D2_Protocol_Tracked Changes_2023-508532-56-00 | 10-1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement_UZ Leuven | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 2.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 3.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_Tracked Changes | 3.0 |
| Recruitment arrangements (for publication) | L1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | LIMIT_Screening Wall Chart_v1-0_2024-09-30_Italian | 1.0 |
| Recruitment arrangements (for publication) | LIMIT_Screening Wall Chart_v1-0_2024-09-30_Italian | 1.0 |
| Recruitment arrangements (for publication) | Patient Facing Letter_pdf | 1 |
| Recruitment arrangements (for publication) | Patient Facing Letter_pdf | 1 |
| Recruitment arrangements (for publication) | Patient Facing Letter_word | 1 |
| Recruitment arrangements (for publication) | Patient Facing Letter_word | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 4.6 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 3.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_CI Actualizado_Word | 5.5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_CI_Actualizado_Tracked Changes | 5.5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Clean | 3.7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Consent | 10.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Consent_Tracked Changes | 10.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Data Consent | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Dine rettigheder som forsgsperson i forsg med medicin_Append to ICF | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_German | 10.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_German Revised | 10.4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_German Revised Tracked Changes | 10.4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Participant Information Sheet | 10.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Participant Information Sheet_Tracked Changes | 10.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_pdf | 10.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Tracked Changes_pdf | 10.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Tracked Changes_word | 10.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_UZ Leuven | 3.4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_word | 10.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_ZOL Genk | 3.4 |
| Subject information and informed consent form (for publication) | L2_LIMIT_Screening Wall Chart | 2.0 |
| Subject information and informed consent form (for publication) | L2_LIMIT_Screening Wall Chart_Tracked Changes | 2.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_GP Letter | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_GP Letter_pdf | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_GP_Letter | 3.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_GP_Letter_Tracked Changes | 3.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Patient Invitation Letter_pdf | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Patient Invitation Letter_word | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Screening Wall Chart | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Screening Wall Chart | 1 |
| Subject information and informed consent form (for publication) | L2_Other subjet information material_GP_Letter_Belgian | 2.0 |
| Subject information and informed consent form (for publication) | L2_Other subjet information material_GP_Letter_Tracked Changes | 2.0 |
| Subject information and informed consent form (for publication) | LIMIT Study Information Card_v1-0_2025-03-20_Danish | 1 |
| Subject information and informed consent form (for publication) | LIMIT_Patient Invitation Letter | 2.0 |
| Subject information and informed consent form (for publication) | LIMIT_Patient Invitation Letter_Tracked Changes | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Rationale IMPs and dosage LIMIT_Belgium | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Rationale IMPs_ dosage LIMIT_Belgium | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Aldocumar | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Aldocumar | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Aldocumar_1mg 3mg 5mg 10mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Sintrom | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Sintrom | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Acenocoumarol 1mg Combined | 1.1.1.1-1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Acenocoumarol_1mg Combined | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_AldocumaR | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Aldocumar | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Aldocumar_1mg 3mg 5mg 10mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Aldocumar_1mg 3mg 5mg 10mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Aldocumar_1mg 3mg 5mg_10mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Aldocumar_1mg_3mg 5mg 10mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Aldocumar_1mg3mg 5mg 10mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Falithrom 1andhalf and 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Falithrom 1andhalf and 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Marcumar 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Marcumar 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Marcuphen 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Marcuphen 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Phenprocoumon Acis 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Phenprocoumon Acis 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Phenprogamma 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Phenprogamma 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Phenprocoumon Phenproratiopharm 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Warfarin Coumadin 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany Warfarin Coumadin 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Germany_Phenprocoumon Phenproratiopharm 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar 2care4 ApS | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar 2care4 ApS | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar 3mg Belgium Netherlands | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar Orifarm | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar Orifarm | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar_2care4 ApS | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar_2care4 ApS | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar_3mg Belgium Netherlands | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar_Orifarm | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marcoumar_Orifarm | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marevan 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marevan Abacus | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marevan Abacus | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marevan Orifarm | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marevan_5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marevan_Abacus | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marevan_Abacus | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marevan_Orifarm | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Marevan_Orifarm | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_MarevanOrifarm | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Meris_Sintrom 1mg 4mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Meris_Sintrom 1mg 4mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Meris_Sintrom_1mg 4mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Meris_Sintrom_1mg 4mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Merus Labs_Sintrom 1mg 4mg_En | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Merus Labs_Sintrom 1mg 4mg_It | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Merus Labs_Sintrom 1mg4mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Merus Labs_Sintrom_1mg 4mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Falithrom 1andhalf and 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Falithrom 1andhalf and 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Marcumar 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Marcumar 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Marcuphen 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Marcuphen 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Phenprocoumon Acis 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Phenprocoumon Acis 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Phenprogamma 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Phenprogamma 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Phenproratiopharm 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Phenprocoumon Phenproratiopharm 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Sintrom | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Sintrom | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Teofarma_Coumadin 5mg_En | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Teofarma_Coumadin 5mg_It | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Teofarma_Coumadin_5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Teofarma_Coumadin_5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Therabel_Marevan 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Therabel_Marevan 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Therabel_Marevan 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Therabel_Marevan_5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Therabel_Marevan_5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Therabel_Marevan_5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Viatris_Marcoumar 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Viatris_Marcoumar 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Viatris_Marcoumar 3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Viatris_Marcoumar_3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Viatris_Marcoumar_3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Viatris_Marcoumar_3mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Warfarin Coumadin 5mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Warfarin Coumadin 5mg | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_v7_2023-508532-56-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_v8_2023-508532-56-00 | 8 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_Tracked Changes_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_Tracked Changes_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_Tracked Changes_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_Tracked Changes_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_Tracked Changes_2023-508532-56-00 | 10-1 |
| Synopsis of the protocol (for publication) | D2_Protocol Synopsis_Tracked Changes_2023-508532-56-00 | 10-1 |
Application history
10 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-10-05 | Spain | Acceptable 2023-11-23
|
2023-11-23 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-12-12 | Acceptable | 2024-03-28 | |
| 3 | SUBSEQUENT ADDITION OF MSC | APP-3 | 2024-07-18 | 2024-10-07 | ||
| 4 | SUBSEQUENT ADDITION OF MSC | APP-4 | 2024-07-18 | 2024-10-10 | ||
| 5 | SUBSEQUENT ADDITION OF MSC | APP-5 | 2024-10-03 | 2024-10-18 | ||
| 6 | SUBSEQUENT ADDITION OF MSC | APP-6 | 2024-10-25 | 2024-12-24 | ||
| 7 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-01-23 | Spain | Acceptable 2025-04-22
|
2025-04-23 |
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-06-19 | Acceptable 2025-04-22
|
2025-06-19 | |
| 9 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-06-23 | Acceptable 2025-04-22
|
2025-06-23 | |
| 10 | SUBSTANTIAL MODIFICATION | SM-8 | 2025-11-28 | Spain | Acceptable 2025-12-18
|
2025-12-18 |