Trial Outcomes & Findings for Microvascular and Antiinflammatory Effects of Rivaroxaban Compared to Aspirin in Type-2 Diabetic Patients With Subclinical Inflammation and High Cardiovascular Risk (NCT NCT02164578)

Last Updated: 2023-11-07

Results Overview

Change of maximal postischemic forearm blood flow during reactive hyperaemia after 5 min of forearm ischemia (FBF max. ml/100ml). Difference of change in post-ischemic forearm blood flow measured by venous occlusion plethysmography at baseline and after 20 weeks treatment with rivaroxaban or aspirin.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

179 participants

Primary outcome timeframe

Baseline and week 20

Results posted on

2023-11-07

Participant Flow

From 14th Apr 2015 through 21st Dec 2017, a total of 239 patients were screened at 4 study sites in Germany. Of them, 60 patients did not meet the eligibility criteria. 188 patients were planned to enrol and 80 patients of them should included in the extension period of the study.

179 patients were randomized to one of the two treatment groups, 89 to receive rivaroxaban and 90 to receive acetylsalicylic acid (ASA). In total, 73 patients were included in the extension period, 37 of them received rivaroxaban and 36 received ASA.

Participant milestones

Participant milestones
Measure	Rivaroxaban 5mg b.i.d. for 20 weeks (treatment phase) + additional 32 weeks (extension phase)	Aspirin 100mg once daily for 20 weeks (treatment phase) + additional 32 weeks (extension phase)
Treatment Period STARTED	89	90
Treatment Period COMPLETED	72	79
Treatment Period NOT COMPLETED	17	11
Extension Period STARTED	37	36
Extension Period COMPLETED	30	35
Extension Period NOT COMPLETED	7	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Rivaroxaban 5mg b.i.d. for 20 weeks (treatment phase) + additional 32 weeks (extension phase)	Aspirin 100mg once daily for 20 weeks (treatment phase) + additional 32 weeks (extension phase)
Treatment Period Withdrawal by Subject	3	3
Treatment Period Adverse Event	13	6
Treatment Period Early termination due to expiry of study medication	1	0
Treatment Period Protocol Violation	0	2
Extension Period Withdrawal by Subject	2	0
Extension Period Adverse Event	4	0
Extension Period Expiry of study medication	1	0
Extension Period Protocol Violation	0	1

Baseline Characteristics

Microvascular and Antiinflammatory Effects of Rivaroxaban Compared to Aspirin in Type-2 Diabetic Patients With Subclinical Inflammation and High Cardiovascular Risk

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rivaroxaban n=89 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=90 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Total n=179 Participants Total of all reporting groups
Age, Continuous	64.2 years n=5 Participants	64.7 years n=7 Participants	64.4 years n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	44 Participants n=7 Participants	95 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	46 Participants n=7 Participants	84 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	89 Participants n=5 Participants	90 Participants n=7 Participants	179 Participants n=5 Participants
Region of Enrollment Germany	89 participants n=5 Participants	90 participants n=7 Participants	179 participants n=5 Participants
BMI	33.2 kg/m^2 n=5 Participants	33.4 kg/m^2 n=7 Participants	33.3 kg/m^2 n=5 Participants
Duration of diabetes	9.21 years n=5 Participants	9.24 years n=7 Participants	9.22 years n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 20

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Rivaroxaban n=83 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=84 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Change in Post-ischemic Forearm Blood Flow	3.60 ml/100ml Standard Deviation 4.69	1.00 ml/100ml Standard Deviation 5.27

PRIMARY outcome

Timeframe: Baseline and week 52

Population: Full Analysis Set of the extension phase

Change in pulse wave velocity as a marker of arterial stiffness (measured by IEM Mobil-O-Graph)

Outcome measures

Outcome measures
Measure	Rivaroxaban n=34 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=36 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Change in Pulse Wave Velocity	0.24 m/s Standard Deviation 0.62	0.51 m/s Standard Deviation 0.57

SECONDARY outcome

Timeframe: Baseline and week 52

Population: Full Analysis Set of the extension phase

Difference of change in post-ischemic forearm blood flow measured by venous occlusion plethysmography at baseline and after 52 weeks treatment with rivaroxaban or aspirin.

Outcome measures

Outcome measures
Measure	Rivaroxaban n=29 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=30 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Change in Post-ischemic Forearm Blood Flow	6.11 ml/100ml Standard Deviation 8.83	1.56 ml/100ml Standard Deviation 5.34

SECONDARY outcome

Timeframe: Baseline to week 20

Population: Full Analysis Set

Change in pulse wave velocity as a marker for arterial stiffness (measured by IEM Mobil-O-Graph)

Outcome measures

Outcome measures
Measure	Rivaroxaban n=82 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=85 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Change in Pulse Wave Velocity	0.02 m/s Standard Deviation 0.44	0.14 m/s Standard Deviation 0.53

SECONDARY outcome

Timeframe: Baseline to week 20

Population: Full Analysis Set

Change in skin blood flow for assessment of peripheral skin microcirculatory function (measured by laserdopplerfluxmetry; LDF)

Outcome measures

Outcome measures
Measure	Rivaroxaban n=76 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=79 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Change in Skin Blood Flow	3.47 arbitrary units Standard Deviation 44.7	-6.01 arbitrary units Standard Deviation 34.0

SECONDARY outcome

Timeframe: Baseline to week 52

Population: Full Analysis Set of the extension phase

Change in skin blood flow for assessment of peripheral skin microcirculatory function (measured by laserdopplerfluxmetry; LDF)

Outcome measures

Outcome measures
Measure	Rivaroxaban n=34 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=36 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Change in Skin Blood Flow	-7.3 arbitrary units Standard Deviation 45.1	5.8 arbitrary units Standard Deviation 59.5

SECONDARY outcome

Timeframe: Week 1 to week 20

Population: Safety Analysis Set

Major bleeding defined as clinically overt and associated with one of the following: 1) reduction of hemoglobin level of 2 g/L or 2) required transfusion of at least 2 units of red cells or, involved a critical organ or was fatal, in accordance with the recommendation of the International Society on Thrombosis and Hemostasis (ISTH).

Outcome measures

Outcome measures
Measure	Rivaroxaban n=89 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=90 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Major Bleeding	1 events	0 events

SECONDARY outcome

Timeframe: Week 1 to week 52

Population: Safety Analysis Set of the extension phase

Outcome measures

Outcome measures
Measure	Rivaroxaban n=37 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=36 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Major Bleeding	0 events	0 events

SECONDARY outcome

Timeframe: Week 1 to week 20

Population: Safety Analysis Set

Clinically relevant non-major (CRNM) bleeding defined as at least one of the following: * spontaneous skin hematoma of at least 25 cm * spontaneous nose bleeding of more than 5 minutes duration * macroscopic hematuria, either spontaneous or, if associated with an intervention, lasting more than 24 hours * spontaneous rectal bleeding (more than spotting on toilet paper) * gingival bleeding for more than 5 minutes * bleeding leading to hospitalization and/or requiring surgical treatment * bleeding leading to a transfusion of less than 2 units of whole blood or red cells * any other bleeding event considered clinically relevant by the investigator

Outcome measures

Outcome measures
Measure	Rivaroxaban n=89 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=90 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Clinically Relevant Non-major (CRNM) Bleeding	11 events	1 events

SECONDARY outcome

Timeframe: Week 1 to week 52

Population: Safety Analysis Set of the extension phase

Outcome measures

Outcome measures
Measure	Rivaroxaban n=37 Participants 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=36 Participants 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Clinically Relevant Non-major (CRNM) Bleeding	6 events	1 events

Adverse Events

Rivaroxaban

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Aspirin

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Dr. Frank Pistrosch

Medical Clinic III, Universitätsklinikum Carl Gustav Carus, Dresden, Germany

Phone: 0049 351 458

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Rivaroxaban n=89 participants at risk 5mg b.i.d. for 20 weeks (primary phase) + additional 32 weeks (extension phase)	Aspirin n=90 participants at risk 100mg once daily for 20 weeks (primary phase) + additional 32 weeks (extension phase)
Gastrointestinal disorders Gastrointestinal hemorrhage	1.1% 1/89 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Gastrointestinal disorders Nausea	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	1.1% 1/90 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Gastrointestinal disorders Vomiting	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	1.1% 1/90 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
General disorders Chest pain	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	1.1% 1/90 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Hepatobiliary disorders Bile duct stone	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	1.1% 1/90 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Infections and infestations Diverticulitis	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	1.1% 1/90 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Infections and infestations Erysipelas	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	1.1% 1/90 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Infections and infestations Escherichia sepsis	1.1% 1/89 • Number of events 2 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Injury, poisoning and procedural complications Foot fracture	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	1.1% 1/90 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	1.1% 1/90 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Musculoskeletal and connective tissue disorders Osteoarthritis	1.1% 1/89 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	1.1% 1/89 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Nervous system disorders Cerebrovascular accident	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	1.1% 1/90 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Nervous system disorders Syncope	1.1% 1/89 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Reproductive system and breast disorders Ovarian cyst	1.1% 1/89 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Respiratory, thoracic and mediastinal disorders Asthma	1.1% 1/89 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Surgical and medical procedures Hysterectomy	1.1% 1/89 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Surgical and medical procedures Joint arthroplasty	1.1% 1/89 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Vascular disorders Hypertension	1.1% 1/89 • Number of events 1 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	0.00% 0/90 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)
Vascular disorders Hypertensive crisis	0.00% 0/89 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)	2.2% 2/90 • Number of events 3 • Randomization to Week 20 (primary phase) and to Week 52 (extension phase)