Clinical trial • Phase IV • Cardiology

APIXABAN for Venous thromboembolism

Phase IV trial of APIXABAN for Venous thromboembolism.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Venous thromboembolism
Trial Stage
Phase IV
Drug Modality
Small molecule|Peptide/protein/enzyme|Other

Key dates

Initial CTIS Submission Date
29-04-2024
First CTIS Authorization Date
12-08-2024

Trial design

Randomised, open-label, comparators include: nadroparin calcium (solution for injection in pre-filled syringe; max daily dose examples in documentation: 2850 iu, 5700 iu), dalteparin sodium (solution for injection in pre-filled syringe; max daily dose examples: 2500 iu, 5000 iu), dabigatran (capsule; max daily dose 220 mg), enoxaparin sodium (solution for injection in pre-filled syringe; max daily dose examples: 2000 iu, 4000 iu), rivaroxaban (film coated tablets; max daily dose 10 mg), apixaban (film coated tablets; doses referenced: 5 mg and 10 mg entries). detailed schedules are not specified in the ctis data.-controlled Phase IV trial in Netherlands.

Randomised
Yes
Open Label
Yes
Comparator
Comparators include: NADROPARIN CALCIUM (solution for injection in pre-filled syringe; max daily dose examples in documentation: 2850 IU, 5700 IU), DALTEPARIN SODIUM (solution for injection in pre-filled syringe; max daily dose examples: 2500 IU, 5000 IU), DABIGATRAN (capsule; max daily dose 220 mg), ENOXAPARIN SODIUM (solution for injection in pre-filled syringe; max daily dose examples: 2000 IU, 4000 IU), RIVAROXABAN (film coated tablets; max daily dose 10 mg), APIXABAN (film coated tablets; doses referenced: 5 mg and 10 mg entries). Detailed schedules are not specified in the CTIS data.
Target Sample Size
10078
Trial Duration For Participant
90

Eligibility

Recruits 10078 No vulnerable populations selected; participants must be aged 18 years or older; insufficient mental or physical ability excludes participation; sufficient knowledge of Dutch is required; informed consent is obtained from adult participants (see adult SIS and ICF documents)..

Pregnancy Exclusion
Pregnancy
Vulnerable Population
No vulnerable populations selected; participants must be aged 18 years or older; insufficient mental or physical ability excludes participation; sufficient knowledge of Dutch is required; informed consent is obtained from adult participants (see adult SIS and ICF documents).

Inclusion criteria

  • {"criterion_text":"- Subjects scheduled to undergo an elective Total Hip Arthroplasty or Total Knee Arthroplasty"}
  • {"criterion_text":"- Subjects aged 18 years or older"}

Exclusion criteria

  • {"criterion_text":"- Primary arthroplasty for fractures"}
  • {"criterion_text":"- Patients using thrombocyte aggregation inhibitors that cannot be temporarily discontinued at the discretion of their treating physician"}
  • {"criterion_text":"- Revision surgery"}
  • {"criterion_text":"- Hemiarthroplasty"}
  • {"criterion_text":"- Pregnancy"}
  • {"criterion_text":"- Current use of therapeutic anticoagulant therapy of any type (e.g., LMWH, DOAC, vitamin K antagonist)"}
  • {"criterion_text":"- A contraindication for either study drug"}
  • {"criterion_text":"- Insufficient knowledge of the Dutch language"}
  • {"criterion_text":"- Insufficient mental or physical ability to fulfil trial requirements"}
  • {"criterion_text":"- Active malignancy (i.e. cancer diagnosis within six months before surgery (excluding basal-cell or squamous-cell carcinoma of the skin), recently recurrent or progressive cancer or any cancer that required anti-cancer treatment within six months before surgery)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Number of VTEs in the first 3 months postoperative","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of major bleeds in the first 3 months postoperative.","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Clinically relevant non major bleeding","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Impact of events on QALY’s","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Healthcare costs","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Prosthetic joint infections","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Patient reported outcome measures","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Myocardial infarction","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Ischemic stroke","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Death","definition_or_measurement_approach":""}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
10078
Recruitment Window Months
65
Consent Approach
Informed consent obtained from adult participants (participants must be ≥18 years). Adult Subject Information Sheet (SIS) and Informed Consent Form (ICF) documents are provided (documents titled 'L1_ SIS and ICF adults DISTINCT'). Materials require sufficient knowledge of Dutch (insufficient knowledge of the Dutch language is an exclusion criterion). No assent for minors (children excluded).

Methods

  • Storyboard animation video (title: 'K2_ Recruitment material Storyboard Animation video general') — digital audiovisual material to inform potential participants.
  • Printed flyer (title: 'K2_ Recruitment material flyer') — paper-based recruitment material for patients.
  • Information on LUMC website (title: 'K2_ Recruitment material information website LUMC') — online institutional website information targeting patients in the Netherlands.
  • Recruitment procedure NL (title: 'K1_ recruitment procedure NL') — documented country-specific recruitment procedure for the Netherlands.

Geography

Total Number Of Sites
15
Total Number Of Participants
10078

Netherlands

Earliest CTIS Part Ii Submission Date
25-06-2024
Latest Decision Or Authorization Date
20-03-2026
Processing Time Days
633
Number Of Sites
15
Number Of Participants
10078

Sites

Site Name
Reinier Haga Groep Orthopedisch Centrum B.V.
Department Name
Orthopedic surgery
Principal Investigator Name
S.B.W. Vehmeijer
Principal Investigator Email
s.vehmeijer@rhoc.nl
Contact Person Name
S.B.W. Vehmeijer
Contact Person Email
s.vehmeijer@rhoc.nl
Site Name
St. Antonius Ziekenhuis
Department Name
Orthopedic surgery
Principal Investigator Name
L. Kaas
Principal Investigator Email
L.Kaas@antoniusziekenhuis.nl
Contact Person Name
L. Kaas
Contact Person Email
L.Kaas@antoniusziekenhuis.nl
Site Name
ZorgSaam Ziekenhuis
Department Name
Orthopedic surgery
Principal Investigator Name
M.P. van de Kerkhove
Principal Investigator Email
m.vandekerkhove@zzv.nl
Contact Person Name
M.P. van de Kerkhove
Contact Person Email
m.vandekerkhove@zzv.nl
Site Name
Stichting OLVG
Department Name
Orthopedic surgery
Principal Investigator Name
R.W. Poolman
Principal Investigator Email
r.w.poolman@olvg.nl
Contact Person Name
R.W. Poolman
Contact Person Email
r.w.poolman@olvg.nl
Site Name
Bergman Clinics Nederland B.V.
Department Name
Orthopedic surgery
Principal Investigator Name
J.I. Wiegerinck
Principal Investigator Email
j.wiegerinck@bergmanclinics.nl
Contact Person Name
J.I. Wiegerinck
Contact Person Email
j.wiegerinck@bergmanclinics.nl
Site Name
Stichting Elisabeth-Tweesteden Ziekenhuis
Department Name
Orthopedic surgery
Principal Investigator Name
P.W. van Egmond
Principal Investigator Email
p.vanegmond@etz.nl
Contact Person Name
P.W. van Egmond
Contact Person Email
p.vanegmond@etz.nl
Site Name
Alrijne Zorggroep Stichting
Department Name
Orthopedic surgery
Principal Investigator Name
R. Mahdad
Principal Investigator Email
rmahdad@alrijne.nl
Contact Person Name
R. Mahdad
Contact Person Email
rmahdad@alrijne.nl
Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
Clinical epidemiology
Principal Investigator Name
B. Nemeth
Principal Investigator Email
b.nemeth@lumc.nl
Contact Person Name
B. Nemeth
Contact Person Email
b.nemeth@lumc.nl
Site Name
Zuyderland Medisch Centrum Stichting
Department Name
Orthopedic surgery
Principal Investigator Name
W.L.W. van Hemert
Principal Investigator Email
w.vanhemert@zuyderland.nl
Contact Person Name
W.L.W. van Hemert
Contact Person Email
w.vanhemert@zuyderland.nl
Site Name
Stichting St. Anna Zorggroep
Department Name
Orthopedic surgery
Principal Investigator Name
M. Siebelt
Principal Investigator Email
m.siebelt@st-anna.nl
Contact Person Name
M. Siebelt
Contact Person Email
m.siebelt@st-anna.nl
Site Name
Isala Klinieken Stichting
Department Name
Orthopedic surgery
Principal Investigator Name
H.B. Ettema
Principal Investigator Email
h.b.ettema@isala.nl
Contact Person Name
H.B. Ettema
Contact Person Email
h.b.ettema@isala.nl
Site Name
Bravis Ziekenhuis
Department Name
Orthopedic surgery
Principal Investigator Name
G. Meermans
Principal Investigator Email
geertmeermans@hotmail.com
Contact Person Name
G. Meermans
Contact Person Email
geertmeermans@hotmail.com
Site Name
Equipe Zorgbedrijven Nederland B.V.
Department Name
Orthopedic surgery
Principal Investigator Name
S.B.W. Vehmeijer
Principal Investigator Email
info@equipezorgbedrijven.nl
Contact Person Name
S.B.W. Vehmeijer
Contact Person Email
info@equipezorgbedrijven.nl
Site Name
Gelre Hospitals
Department Name
Orthopedic surgery
Principal Investigator Name
B. Boesenach
Principal Investigator Email
b.boesenach@gelre.nl
Contact Person Name
B. Boesenach
Contact Person Email
b.boesenach@gelre.nl
Site Name
Groene Hart Ziekenhuis
Department Name
Orthopedic surgery
Principal Investigator Name
R. Onstenk
Principal Investigator Email
ron.onstenk@ghz.nl
Contact Person Name
R. Onstenk
Contact Person Email
ron.onstenk@ghz.nl

Sponsor

Primary sponsor

Full Name
Academisch Ziekenhuis Leiden
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Netherlands

Investigational products

Investigational Product Name
APIXABAN
Active Substance
APIXABAN
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
marketingAuthNumber: - (prodAuthStatus: 2)
Maximum Dose
5 mg (entries include 5 mg and 10 mg formulations; maxDailyDoseAmount entries show 5 and 10 mg in product records)
Investigational Product Name
NADROPARIN CALCIUM
Active Substance
NADROPARIN CALCIUM
Modality
Other
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Authorisation Status
marketingAuthNumber: - (prodAuthStatus: 2)
Maximum Dose
examples in product records: 2850 IU, 5700 IU
Investigational Product Name
DALTEPARIN SODIUM
Active Substance
DALTEPARIN SODIUM
Modality
Other
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Authorisation Status
marketingAuthNumber: - (prodAuthStatus: 2)
Maximum Dose
examples in product records: 2500 IU, 5000 IU
Investigational Product Name
ENOXAPARIN SODIUM
Active Substance
ENOXAPARIN SODIUM
Modality
Other
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Authorisation Status
marketingAuthNumber: - (prodAuthStatus: 2)
Maximum Dose
examples in product records: 2000 IU, 4000 IU
Investigational Product Name
DABIGATRAN
Active Substance
DABIGATRAN
Modality
Small molecule
Routes Of Administration
ORAL (capsule)
Route
ORAL
Authorisation Status
marketingAuthNumber: - (prodAuthStatus: 2)
Maximum Dose
maxDailyDoseAmount: 220 mg (as recorded)
Investigational Product Name
RIVAROXABAN
Active Substance
RIVAROXABAN
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
marketingAuthNumber: - (prodAuthStatus: 2)
Maximum Dose
maxDailyDoseAmount: 10 mg (as recorded)
Investigational Product Name
ANDEXANET ALFA
Active Substance
ANDEXANET ALFA
Modality
Peptide/protein/enzyme
Routes Of Administration
INFUSION
Route
INFUSION
Authorisation Status
marketingAuthNumber: - (prodAuthStatus: 2)
Maximum Dose
maxDailyDoseAmount: 1760 mg (as recorded)
Investigational Product Name
Cofact 250 IE (Solution for injection)
Active Substance
HUMAN COAGULATION FACTOR IX; PROTEIN C; HUMAN COAGULATION FACTOR VII; PROTEIN S; HUMAN COAGULATION FACTOR II; HUMAN COAGULATION FACTOR X
Modality
Peptide/protein/enzyme
Routes Of Administration
INFUSION
Route
INFUSION
Authorisation Status
marketingAuthNumber: RVG 17060 (NL/H/0859/001) for Cofact 250 IE
Maximum Dose
maxDailyDoseAmount: 2500 U (as recorded)
Investigational Product Name
Cofact 500 IE (Solution for injection)
Active Substance
HUMAN COAGULATION FACTOR IX; PROTEIN C; HUMAN COAGULATION FACTOR VII; PROTEIN S; HUMAN COAGULATION FACTOR II; HUMAN COAGULATION FACTOR X
Modality
Peptide/protein/enzyme
Routes Of Administration
INFUSION
Route
INFUSION
Authorisation Status
marketingAuthNumber: RVG 17060 (NL/H/0859/002) for Cofact 500 IE
Maximum Dose
maxDailyDoseAmount: 2500 U (as recorded)

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