Comparison of a Rivaroxaban-based Strategy With an Antipl... | NCT02833948

NCT02833948

Status Module

Name	Class
Rigshospitalet, Denmark	OTHER
Bayer	INDUSTRY
Cardialysis BV	INDUSTRY

Oversight Module

Description Module

Detailed Description

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established therapeutic option for patients with symptomatic, severe aortic valve stenosis, who are ineligible or at high risk for conventional surgical aortic valve replacement (SAVR). It was recently reported that leaflet thickening and reduced leaflet motion, verified by four-dimensional computed tomography (4DCT), was not uncommon after both TAVR and SAVR. It has been emphasized that this phenomenon should be further investigated for its effect on clinical outcomes (e.g. stroke) and valve durability. As this valve leaflet thickening and reduced motion could be reversed by oral anticoagulant (OAC) treatment and was not observed in patients on chronic OAC therapy, it has been hypothesized that this phenomenon could be related to possible leaflet thrombosis or a "thrombotic film" on the leaflets.

AIM: To evaluate whether a rivaroxaban-based strategy, following successful TAVR, compared to an antiplatelet-based strategy, is superior in reducing subclinical valve leaflet thickening and motion abnormalities - as detected by 4DCT-scan.

POPULATION: All patients undergoing successful TAVR by ileofemoral or subclavian access with an approved TAVR device will be screened for eligibility. Included subjects must provide written informed consent. Inclusion and exclusion criteria are listed below.

DESIGN: The GALILEO-4D trial will be conducted as a substudy of the multicenter, open-label, randomized, event-driven, active-controlled GALILEO trial. Patients will be 1:1 randomized to an antiplatelet-based strategy vs. rivaroxaban-based strategy - the randomization will adopt the same 1:1 randomization of the main GALILEO trial. In case the GALILEO-4D trial should still be continued after completion of the main GALILEO trial, this 1:1 randomization will be continued until inclusion of 150 patients in both treatment groups. In total, 300 patients will be randomized in the GALILEO-4D trial.

INTERVENTION: Subjects in the GALILEO-4D substudy will receive the same intervention as in the main GALILEO study. In addition, a 4DCT-scan and echocardiography will be performed at 90 days after randomization.

END POINTS: The primary endpoint constitutes the rate of patients with at least one prosthetic leaflet with > 50% motion reduction as assessed by cardiac 4DCT-scan (total N = 300). The secondary endpoints are listed below.

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
ASA + Clopidogrel	Active Comparator	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy	Drug: Acetylsalicylic acid Drug: Clopidogrel
Rivaroxaban + ASA	Experimental	Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy	Drug: Acetylsalicylic acid Drug: Rivaroxaban

Name	Type	Description	Arm Group Labels	Other Names
Acetylsalicylic acid	Drug	Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1)	ASA + Clopidogrel Rivaroxaban + ASA

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Rate of Patients With at Least One Prosthetic Leaflet With >50% Motion Reduction as Assessed by Cardiac 4DCT-scan	Reduced systolic leaflet excursion is classified as: (I) normal, (II) mildly reduced (<50%), (III) moderate to severely reduced (>50%), and (IV) immobile. Reduced systolic leaflet excursion is considered significant when it is > 50% or immobile. Quantitative assessment of leaflet motion is performed with a blood pool inversion volume rendered cine reconstruction throughout the cardiac cycle evaluating the bioprosthetic leaflets.	3 months

Secondary Outcomes

Measure	Description	Time Frame
The Rate of Prosthetic Leaflets With > 50% Motion Reduction as Assessed by Cardiac 4DCT-scan	The rate of prosthetic leaflets with RLM> grade 3 as assessed by cardiac 4DCT	3 months
The Rate of Patients With at Least One Prosthetic Leaflet With Thickening as Assessed by Cardiac 4DCT-scan

Eligibility Module

Name	Affiliation	Role
Lars Søndergaard, MD;DMSc	Rigshospitalet, Denmark	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Cedars Sinai Medical Center		Los Angeles	California	90048	United States
Mount Sinai M.C

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26436963	Background	Makkar RR, Fontana G, Jilaihawi H, Chakravarty T, Kofoed KF, De Backer O, Asch FM, Ruiz CE, Olsen NT, Trento A, Friedman J, Berman D, Cheng W, Kashif M, Jelnin V, Kliger CA, Guo H, Pichard AD, Weissman NJ, Kapadia S, Manasse E, Bhatt DL, Leon MB, Sondergaard L. Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves. N Engl J Med. 2015 Nov 19;373(21):2015-24. doi: 10.1056/NEJMoa1509233. Epub 2015 Oct 5.
31733182

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	ASA + Clopidogrel	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Clopidogrel: Drug: Clopidogrel 75 mg OD for first 90 days If new-onset atrial fibrillation occurred within three months, clopidogrel was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3 and combined with acetylsalicyclic acid 75mg to 100mg once-daily (which was discontinued at three month post-TAVR); however, if new-onset atrial fibrillation occurred after three months, acetylsalicyclic acid 75mg to 100mg once-daily was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 29, 2017

Arm/Group Information

ID	Title	Description
BG000	ASA + Clopidogrel	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Clopidogrel: Drug: Clopidogrel 75 mg OD for first 90 days If new-onset atrial fibrillation occurred within three months, clopidogrel was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3 and combined with acetylsalicyclic acid 75mg to 100mg once-daily (which was discontinued at three month post-TAVR); however, if new-onset atrial fibrillation occurred after three months, acetylsalicyclic acid 75mg to 100mg once-daily was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3.
BG001	Rivaroxaban + ASA	Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Rivaroxaban: Drug: Rivaroxaban (Xarelto): 10 mg OD (once-daily) If new-onset atrial fibrillation occurred within this group, the rivaroxaban drug dose was increased from 10mg once-daily to 20mg once-daily (or 15mg once-daily in patients with moderate renal dysfunction as per drug label) plus acetylsalicyclic acid 75mg to 100mg once-daily; acetylsalicyclic acid was discontinued at three months post-TAVR.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

- ParticipantsBG000116
- ParticipantsBG001115
- ParticipantsBG002231

Title	Measurements

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Race and Ethnicity Not Collected

Race and Ethnicity were not collected from any participant.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG0000 ParticipantsBG0010 ParticipantsBG002

Body-mass index

Mean

Standard Deviation

kg/m^2

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Hypertension

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Diabetes Mellitus

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

STS risk score

Mean

Standard Deviation

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

STS risk category - High

The risk model of the Society of Thoracic Surgeons (STS) uses an algorithm that is based on the presence of coexisting illnesses to predict 30-day operative mortality. The STS score equals the predicted mortality expressed as a percentage.

A score of greater than 8% indicates high risk, 3 to 8% intermediate risk, and les than 3% low risk.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

STS risk category - Intemediate

A score of greater than 8% indicates high risk, 3 to 8% intermediate risk, and les than 3% low risk.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

STS risk category - low

A score of greater than 8% indicates high risk, 3 to 8% intermediate risk, and les than 3% low risk.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Congestive Heart Failure

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Coronary Artery Disease

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Previous stroke

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Peripheral Artery disease

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Previous venous thromboembolism

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Permanent Pacemaker

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Chronic obstructive pulmonary disease

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Glomerular filtration rate

Mean

Standard Deviation

ml/min/1.73m2

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Valve type - balloon-expandable

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Valve type - Self-expandable

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Valve type - Supra-annular leaflet position

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Valve-in-valve

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Post TAVR Echo - Aortic-valve-area

Mean

Standard Deviation

cm2

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Post TAVR Echo - mean aortic-valve gradient

Mean

Standard Deviation

mm Hg

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Post TAVR Echo - Left Ventricular ejection fraction

Mean

Standard Deviation

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Paravalvular aortic regurgitation - none or trace

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Paravalvular aortic regurgitation - Mild

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Paravalvular aortic regurgitation - moderate or severe

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001115 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Rate of Patients With at Least One Prosthetic Leaflet With >50% Motion Reduction as Assessed by Cardiac 4DCT-scan

Reduced systolic leaflet excursion is classified as: (I) normal, (II) mildly reduced (<50%), (III) moderate to severely reduced (>50%), and (IV) immobile. Reduced systolic leaflet excursion is considered significant when it is > 50% or immobile. Quantitative assessment of leaflet motion is performed with a blood pool inversion volume rendered cine reconstruction throughout the cardiac cycle evaluating the bioprosthetic leaflets.

Intention-to-treat (ITT) study population

Posted

Count of Participants

Participants

3 months

ID	Title	Description
OG000	ASA + Clopidogrel	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Clopidogrel: Drug: Clopidogrel 75 mg OD for first 90 days If new-onset atrial fibrillation occurred within three months, clopidogrel was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3 and combined with acetylsalicyclic acid 75mg to 100mg once-daily (which was discontinued at three month post-TAVR); however, if new-onset atrial fibrillation occurred after three months, acetylsalicyclic acid 75mg to 100mg once-daily was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3.
OG001	Rivaroxaban + ASA	Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Rivaroxaban: Drug: Rivaroxaban (Xarelto): 10 mg OD (once-daily) If new-onset atrial fibrillation occurred within this group, the rivaroxaban drug dose was increased from 10mg once-daily to 20mg once-daily (or 15mg once-daily in patients with moderate renal dysfunction as per drug label) plus acetylsalicyclic acid 75mg to 100mg once-daily; acetylsalicyclic acid was discontinued at three months post-TAVR.

Units	Counts
Participants	OG000101 OG00197

Title

Denominators

Categories

Title	Measurements
	OG00011 OG0012

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact	The Fisher's exact probability test was used to compare the percentages of patients with the primary end point between the treatment groups.	0.01														Superiority

Secondary

The Rate of Prosthetic Leaflets With > 50% Motion Reduction as Assessed by Cardiac 4DCT-scan

The rate of prosthetic leaflets with RLM> grade 3 as assessed by cardiac 4DCT

Intention-to-treat (ITT) study population

Posted

Number

leaflets

3 months

leaflets

ID	Title	Description
OG000	ASA + Clopidogrel	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Clopidogrel: Drug: Clopidogrel 75 mg OD for first 90 days If new-onset atrial fibrillation occurred within three months, clopidogrel was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3 and combined with acetylsalicyclic acid 75mg to 100mg once-daily (which was discontinued at three month post-TAVR); however, if new-onset atrial fibrillation occurred after three months, acetylsalicyclic acid 75mg to 100mg once-daily was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3.
OG001	Rivaroxaban + ASA	Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Rivaroxaban: Drug: Rivaroxaban (Xarelto): 10 mg OD (once-daily) If new-onset atrial fibrillation occurred within this group, the rivaroxaban drug dose was increased from 10mg once-daily to 20mg once-daily (or 15mg once-daily in patients with moderate renal dysfunction as per drug label) plus acetylsalicyclic acid 75mg to 100mg once-daily; acetylsalicyclic acid was discontinued at three months post-TAVR.

Secondary

The Rate of Patients With at Least One Prosthetic Leaflet With Thickening as Assessed by Cardiac 4DCT-scan

The rate of patients with at least one prosthetic leaflet with hypoattenuated leaflet thickening (HALT) as assessed by cardiac 4DCT.

Intention-to-treat (ITT) study population

Posted

Count of Participants

Participants

3 months

ID	Title	Description
OG000	ASA + Clopidogrel	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Clopidogrel: Drug: Clopidogrel 75 mg OD for first 90 days If new-onset atrial fibrillation occurred within three months, clopidogrel was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3 and combined with acetylsalicyclic acid 75mg to 100mg once-daily (which was discontinued at three month post-TAVR); however, if new-onset atrial fibrillation occurred after three months, acetylsalicyclic acid 75mg to 100mg once-daily was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3.
OG001	Rivaroxaban + ASA	Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Rivaroxaban: Drug: Rivaroxaban (Xarelto): 10 mg OD (once-daily) If new-onset atrial fibrillation occurred within this group, the rivaroxaban drug dose was increased from 10mg once-daily to 20mg once-daily (or 15mg once-daily in patients with moderate renal dysfunction as per drug label) plus acetylsalicyclic acid 75mg to 100mg once-daily; acetylsalicyclic acid was discontinued at three months post-TAVR.

Secondary

The Rate of Prosthetic Leaflets With Thickening as Assessed by Cardiac 4DCT-scan

The rate of prosthetic leaflet with HALT as assessed by cardiac 4DCT-scan

Intention-to-treat (ITT) study population

Posted

Number

Leaflets

3 months

Leaflets

ID	Title	Description
OG000	ASA + Clopidogrel	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Clopidogrel: Drug: Clopidogrel 75 mg OD for first 90 days If new-onset atrial fibrillation occurred within three months, clopidogrel was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3 and combined with acetylsalicyclic acid 75mg to 100mg once-daily (which was discontinued at three month post-TAVR); however, if new-onset atrial fibrillation occurred after three months, acetylsalicyclic acid 75mg to 100mg once-daily was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3.
OG001	Rivaroxaban + ASA	Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Rivaroxaban: Drug: Rivaroxaban (Xarelto): 10 mg OD (once-daily) If new-onset atrial fibrillation occurred within this group, the rivaroxaban drug dose was increased from 10mg once-daily to 20mg once-daily (or 15mg once-daily in patients with moderate renal dysfunction as per drug label) plus acetylsalicyclic acid 75mg to 100mg once-daily; acetylsalicyclic acid was discontinued at three months post-TAVR.

Secondary

Aortic Transvalvular Mean Pressure Gradient (mmHg) as Determined by Transthoracic Echocardiography.

Transprosthetic mean pressure gradiënt as determined by transthoracic echocardiography at three months after randomization.

scale [0-100]

Intention-to-treat (ITT) study population

Posted

Mean

Standard Deviation

mm Hg

3 months

ID	Title	Description
OG000	ASA + Clopidogrel	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Clopidogrel: Drug: Clopidogrel 75 mg OD for first 90 days If new-onset atrial fibrillation occurred within three months, clopidogrel was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3 and combined with acetylsalicyclic acid 75mg to 100mg once-daily (which was discontinued at three month post-TAVR); however, if new-onset atrial fibrillation occurred after three months, acetylsalicyclic acid 75mg to 100mg once-daily was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3.
OG001	Rivaroxaban + ASA	Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Rivaroxaban: Drug: Rivaroxaban (Xarelto): 10 mg OD (once-daily) If new-onset atrial fibrillation occurred within this group, the rivaroxaban drug dose was increased from 10mg once-daily to 20mg once-daily (or 15mg once-daily in patients with moderate renal dysfunction as per drug label) plus acetylsalicyclic acid 75mg to 100mg once-daily; acetylsalicyclic acid was discontinued at three months post-TAVR.

Secondary

Effective Orifice Area (cm^2) as Determined by Transthoracic Echocardiography.

Effective orifice area (cm2) as determined by transthoracic echocardiography at three months after randomization.

scale [0.1-4.0]

Intention-to-treat (ITT) study population

Posted

Mean

Standard Deviation

cm2

3 months

ID	Title	Description
OG000	ASA + Clopidogrel	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Clopidogrel: Drug: Clopidogrel 75 mg OD for first 90 days If new-onset atrial fibrillation occurred within three months, clopidogrel was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3 and combined with acetylsalicyclic acid 75mg to 100mg once-daily (which was discontinued at three month post-TAVR); however, if new-onset atrial fibrillation occurred after three months, acetylsalicyclic acid 75mg to 100mg once-daily was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3.
OG001	Rivaroxaban + ASA	Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Rivaroxaban: Drug: Rivaroxaban (Xarelto): 10 mg OD (once-daily) If new-onset atrial fibrillation occurred within this group, the rivaroxaban drug dose was increased from 10mg once-daily to 20mg once-daily (or 15mg once-daily in patients with moderate renal dysfunction as per drug label) plus acetylsalicyclic acid 75mg to 100mg once-daily; acetylsalicyclic acid was discontinued at three months post-TAVR.

Secondary

Death Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (HALT) - as Exploratory Analysis.

Death, Dichotomization by HALT

Intention-to-treat (ITT) study population, subgroup of patients with analysable scans

Posted

Count of Participants

Participants

3 months

ID	Title	Description
OG000	HALT (-)	Hypoattenuated leaflet thickening (-)
OG001	HALT (+)	Hypoattenuated leaflet thickening (+)

Units	Counts
Participants	OG000

Secondary

Death Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (RLM)- as Exploratory Analysis.

Death, Dichotomization by RLM

Intention-to-treat (ITT) study population, subgroup of patients with analysable scans

Posted

Count of Participants

Participants

3 months

ID	Title	Description
OG000	RLM>2 (-)	Reduced Leaflet Motion >2 (-)
OG001	RLM(+)	Reduced Leaflet Motion >2 (+)

Units	Counts
Participants	OG000

Secondary

Thromboembolic Event Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (HALT)- as Exploratory Analysis.

Thromboembolic event, Dichotomization by HALT

Intention-to-treat (ITT) study population, subgroup of patients with analysable scans

Posted

Count of Participants

Participants

3 months

ID	Title	Description
OG000	HALT (-)	Hypoattenuated leaflet thickening (-)
OG001	HALT (+)	Hypoattenuated leaflet thickening (+)

Units	Counts
Participants	OG000

Secondary

Thromboembolic Event Assessed in the Main GALILEO Study and Analyzed in the GALILEO-4D Substudy With Regards to Occurence of the Leaflet Abnormalities (RLM) - as Exploratory Analysis.

Thromboembolic event, Dichotomization by RLM

Intention-to-treat (ITT) study population, subgroup of patients with analysable scans

Posted

Count of Participants

Participants

3 months

ID	Title	Description
OG000	RLM>2 (-)	Reduced Leaflet Motion >2 (-)
OG001	RLM(+)	Reduced Leaflet Motion >2 (+)

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ASA + Clopidogrel	ASA (Acetylsalicylic acid) 75-100mg + Clopidogrel 75mg for 90 days, followed by ASA 75-100mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Clopidogrel: Drug: Clopidogrel 75 mg OD for first 90 days If new-onset atrial fibrillation occurred within three months, clopidogrel was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3 and combined with acetylsalicyclic acid 75mg to 100mg once-daily (which was discontinued at three month post-TAVR); however, if new-onset atrial fibrillation occurred after three months, acetylsalicyclic acid 75mg to 100mg once-daily was replaced by vitamin K antagonist targeting an international normalized ratio of 2 to 3.	2	116	3	116	17	116
EG001	Rivaroxaban + ASA	Rivaroxaban 10mg + ASA 75-100mg for 90 days, followed by rivaroxaban 10mg monotherapy Acetylsalicylic acid: Drug: Acetylsalicylic acid: 75 - 100 mg OD (for first 90 days only in arm 1) Rivaroxaban: Drug: Rivaroxaban (Xarelto): 10 mg OD (once-daily) If new-onset atrial fibrillation occurred within this group, the rivaroxaban drug dose was increased from 10mg once-daily to 20mg once-daily (or 15mg once-daily in patients with moderate renal dysfunction as per drug label) plus acetylsalicyclic acid 75mg to 100mg once-daily; acetylsalicyclic acid was discontinued at three months post-TAVR.	3	115	7	115	16	115

Ancestor Terms

ID	Term
D012459	Salicylates
D062385	Hydroxybenzoates
D010636	Phenols
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D013988	Ticlopidine
D058924	Thienopyridines
D013876	Thiophenes
D013457	Sulfur Compounds
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D009025	Morpholines
D010078	Oxazines

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Major bleeding event	Blood and lymphatic system disorders		Systematic Assessment		EG0001 events1 affected116 at risk EG0014 events4 affected115 at risk
Thromboembolic event	Cardiac disorders		Systematic Assessment		EG0002 events2 affected116 at risk EG0014 events4 affected115 at risk

ID	Term
D001024	Aortic Valve Stenosis
D002318	Cardiovascular Diseases
D006349	Heart Valve Diseases
D014694	Ventricular Outflow Obstruction
D013927	Thrombosis

ID	Term
D000082862	Aortic Valve Disease
D006331	Heart Diseases
D016769	Embolism and Thrombosis
D014652	Vascular Diseases

ID	Term
D001241	Aspirin
C010395	acetylsalicylic acid lysinate
D000077144	Clopidogrel
D000069552	Rivaroxaban