Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ended
Participants planned
2,276
Countries
1
Sites
17
Peripheral Arterial Disease
to evaluate the ability of genotypeguided antithrombotic treatment to reduce adverse clinical events related to arterial thrombosis in PAD patients. Adverse clinical events of interest are major adverse cardiovascular events (myocardial infarction, stroke, transient ischemic arrack), major adverse limb events (acute/c…
Key facts
- Sponsor
- Radboud universitair medisch centrum Stichting
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 13 Dec 2024 → 6 May 2025
- Decision date (initial)
- 2024-12-13
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-518122-33-00
- EudraCT number
- 2020-004913-11
- ClinicalTrials.gov
- NCT04619927
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy
to evaluate the ability of genotypeguided antithrombotic treatment to reduce adverse clinical events related to arterial thrombosis in PAD patients. Adverse clinical events of interest are major adverse
cardiovascular events (myocardial infarction, stroke, transient ischemic arrack), major adverse limb events (acute/chronic limb ischemia of peripheral vascular intervention including amputation) and death.
Conditions and MedDRA coding
Peripheral Arterial Disease
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Age > 16 years
- Indication for monotherapy clopidogrel 75mg once daily
- Ankle-brachial index < 0.9 and/or toe brachial index < 0.5
- Current or previous symptoms due to insufficient vascularization of one or two lower extremities, including intermittent claudication, pain at rest and/or gangrene (Rutherford category 1-6)
- Consulting a vascular surgeon for diagnosis, treatment and/or follow-up of PAD
Exclusion criteria 4
- known CYP2C19 genotype or metabolizer state
- treated with coumarins, Non-vitamin K Oral Anti-Coagulants, unfractionated heparin, low molecular weight heparins or double antiplatelet therapy with acetylsalicylic acid and a P2Y12 inhibitor for other indications
- contraindication for clopidogrel, acetylsalicylic acid and/or rivaroxaban
- pregnant or breastfeeding women
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary outcome is the occurrence of adverse clinical events related to arterial thrombosis at 24 months, including death from any cause, major adverse cardiovascular events (MACE) and major adverse limb events (MALE).
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
SCP100377272 · ATC
- Active substance
- Lactose Monohydrate
- Substance synonyms
- LACTOSE hydrate
- Route of administration
- ORAL
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 5 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF01 — RIVAROXABAN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP131039 · ATC
- Active substance
- Carbasalate Calcium
- Substance synonyms
- Carbaspirin calcium
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 100 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AC06 — ACETYLSALICYLIC ACID
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1108233 · ATC
- Active substance
- Telmisartan
- Route of administration
- ORAL
- Max daily dose
- 75 mg milligram(s)
- Max total dose
- 75 mg milligram(s)
- Max treatment duration
- 36 Week(s)
- Authorisation status
- Authorised
- ATC code
- B01AC04 — CLOPIDOGREL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Radboud universitair medisch centrum Stichting
- Sponsor organisation
- Radboud universitair medisch centrum Stichting
- Address
- Geert Grooteplein Zuid 10
- City
- Nijmegen
- Postcode
- 6525 GA
- Country
- Netherlands
Scientific contact point
- Organisation
- Radboud universitair medisch centrum Stichting
- Contact name
- Michiel Warle
Public contact point
- Organisation
- Radboud universitair medisch centrum Stichting
- Contact name
- Marjan de Vries
Locations
1 EU/EEA country · 17 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 2,276 | 17 |
| Rest of world | — | 0 | — |
Investigational sites
Ziekenhuis Gelderse Vallei
chirurgie, Wille Brandtlaan 10, 6716 RP, Ede
Stichting Viecuri Medisch Centrum voor Noord-Limburg
chirurgie, Tegelseweg 210, 5912 BL, Venlo
Gelre Hospitals
chirurgie, Albert Schweitzerlaan 31, 7334 DZ, Apeldoorn
Dijklander Ziekenhuis
chirurgie, Maelsonstraat 3, 1624 NP, Hoorn Nh
Amsterdam UMC Stichting
chirurgie, Meibergdreef 9, 1105 AZ, Amsterdam
Rijnstate Ziekenhuis Stichting
chirurgie, Wagnerlaan 55, 6815 AD, Arnhem
Radboud universitair medisch centrum Stichting
chirurgie, P. O. Box 9101, 6500 HB, Nijmegen
Ommelander Ziekenhuis Groningen B.V.
chirurgie, Pastorieweg 1, 9679 BJ, Scheemda
Bernhoven B.V.
chirurgie, Nistelrodeseweg 10, 5406 PT, Uden
Groene Hart Ziekenhuis
chirurgie, Bleulandweg 10, 2803 HH, Gouda
Slingeland Ziekenhuis
chirurgie, Kruisbergseweg 25, 7009 BL, Doetinchem
Maxima Medisch Centrum
chirurgie, Ds Theodor Fliednerstraat 1, 5631 BM, Eindhoven
Universitair Medisch Centrum Groningen
chirurgie, Hanzeplein 1, 9713 GZ, Groningen
Canisius Wilhelmina Ziekenhuis
chirurgie, Weg Door Jonkerbos 100, 6532 SZ, Nijmegen
Academisch Ziekenhuis Maastricht
chirurgie, P Debyelaan 25, 6229 HX, Maastricht
Medisch Spectrum Twente
chirurgie, Koningsplein 1, 7512 KZ, Enschede
Maasziekenhuis Pantein B.V.
chirurgie, Dokter Kopstraat 1, 5835 DV, Beugen
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 |
|---|---|---|---|---|---|
| Netherlands | 2024-12-13 | 2025-05-06 | 2024-12-13 | 2024-12-13 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-86495
- Sponsor became aware
- 2025-06-10
- Date of breach
- 2023-08-22
- Submission date
- 2025-06-13
- Member states concerned
- Netherlands
- Categories
- Regulation
- Areas impacted
- Subject rights, Regulatory
- Benefit-risk balance changed
- No
- Description
- A previous version of the Patient Information Form (PIF) was used for participant inclusion at one of the participating sites. The primary difference between the outdated and current versions of the PIF concerns the method of inclusion and sample collection for CYP2C19 genotyping. The most recent PIF specifies the use of remote inclusion via saliva kits, whereas the earlier version described blood sampling as the primary method, with remote inclusion also being possible (e.g. patient preference or absence of further hospital visits).
Although the outdated PIF did still allow for remote inclusion, it did not reflect the newest approved approach described in the latest version submitted to the authorities. As a result, participants at this site were consented based on slightly outdated information regarding the sample collection procedure. This constitutes a deviation from the approved protocol and the authorized patient information, and is therefore being reported as a serious breach in accordance with regulatory requirements. - Sponsor actions
- The use of the outdated version of the Patient Information Form (PIF) at this participating site was discovered after the inclusion period of the trial had ended. As a result, no new participants were included using the outdated document after the issue was identified.
The outdated PIF differed from the approved version mainly in the description of the sample collection method for CYP2C19 genotyping (blood sampling as the standard versus remote saliva collection). Although the outdated version still allowed for remote inclusion, it did not reflect the final approved approach as communicated in the most recent PIF.
There is no indication that participants were exposed to increased risk or that their rights were compromised. Data integrity is considered unaffected. However, the use of an outdated PIF version represents a deviation from Good Clinical Practice and applicable regulatory requirements, as participants were not consented using the most recently approved information.
| Organisation | City | Country | Type |
|---|---|---|---|
| Medisch Spectrum Twente | Enschede | Netherlands | Clinical investigator |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ protocol 2024-518122-33 | 3 |
| Recruitment arrangements (for publication) | K1_blank_document_Recruitment_arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and GENPAD | 2.2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC Aspirin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC clopidogrel | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC rivaroxaban | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-14 | Netherlands | Acceptable 2024-12-13
|
2024-12-13 |