Trial Outcomes & Findings for Pilot Study to Examine the Use of Rivaroxaban After Angioplasty for Critical Limb Ischemia (NCT NCT02260622)

NCT ID: NCT02260622

Last Updated: 2019-12-04

Results Overview

The primary outcome is a combined endpoint consisting of any Reintervention (surgical procedures to revascularize), Above ankle amputation and restenosis(recurrence of blockage in the vein) (RAS) at one year

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2019-12-04

Participant Flow

Participant milestones

Measure	Clopidogrel Plus Aspirin Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Overall Study STARTED	11	9
Overall Study COMPLETED	11	9
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pilot Study to Examine the Use of Rivaroxaban After Angioplasty for Critical Limb Ischemia

Baseline characteristics by cohort

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days	Total n=20 Participants Total of all reporting groups
Age, Continuous	74.8 years n=5 Participants	59.5 years n=7 Participants	67 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

The primary outcome is a combined endpoint consisting of any Reintervention (surgical procedures to revascularize), Above ankle amputation and restenosis(recurrence of blockage in the vein) (RAS) at one year

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Reintervention, Above Ankle Amputation and Restenosis (RAS)	7 Participants	4 Participants

SECONDARY outcome

Timeframe: 1 year

Clinical improvement defined as cumulative improvement of 2 classes of the Rutherford scale without the need for repeated TLR in surviving patients.

There are seven stages to consider. the lower the score the less severe the disease or condition.

Rutherford Scale:

Stage 0 - Asymptomatic Stage 1 - Mild claudication Stage 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters.

Stage 3 - Severe claudication Stage 4 - Rest pain Stage 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Stage 6 - Severe ischemic ulcers or frank gangrene

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Number of Participants With 2 Class Improvement on the Rutherford Scale	5 Participants	8 Participants

SECONDARY outcome

Timeframe: 1 year

Event-free survival How long a patient is alive without the need for any further intervention or vascular events.

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Event-free Survival	4 Participants	4 Participants

SECONDARY outcome

Timeframe: 1 year

Overall survival. How long a patient is alive following the intervention.

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Overall Survival	11 Participants	9 Participants

SECONDARY outcome

Timeframe: 1 year

Target lesion revascularization (TLR) between day 1 and final visit

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
The Number of Patients Requiring Target Lesions Revascularization Between Day 1 and the Final Visit (TLR)	2 Participants	1 Participants

SECONDARY outcome

Timeframe: 1 year

Target vessel revascularization (TVR between day 1 and final visit)

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
TVR	2 Participants	1 Participants

SECONDARY outcome

Timeframe: 30 days

The number of patients that die within 30 days of the revascularization procedure.

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Peri-procedure Death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1 year

Cumulative rate of major adverse cardiovascular events between day 1 and final visit

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
MACE	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 90 days

Cumulative rate of major bleeding between day 1 and day 90

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Major Bleeding	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 90 days

Cumulative clinically relevant or minor bleeding between day 1 and day 90

Outcome measures

Measure	Clopidogrel Plus Aspirin n=11 Participants Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 Participants Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Minor Bleeding	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 90 days

Population: Not performed.

Biological plausibility by measuring coagulation changes and SMC proliferation markers within 7 and 90 days based on the following markers: D-dimer, soluble CD40/44 ligands, and ERK 1/2

Outcome measures

Outcome data not reported

Adverse Events

Clopidogrel Plus Aspirin

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Rivaroxaban Plus Aspirin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Clopidogrel Plus Aspirin n=11 participants at risk Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily clopidogrel plus aspirin: Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days	Rivaroxaban Plus Aspirin n=9 participants at risk Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily rivaroxaban plus aspirin: Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Musculoskeletal and connective tissue disorders Leg injury	9.1% 1/11 • Number of events 1 • From randomization to 12-month follow-up	11.1% 1/9 • Number of events 1 • From randomization to 12-month follow-up
Investigations Abnormal Lab Result	9.1% 1/11 • Number of events 1 • From randomization to 12-month follow-up	0.00% 0/9 • From randomization to 12-month follow-up
Blood and lymphatic system disorders Minor Bleed - not clinically relevant	0.00% 0/11 • From randomization to 12-month follow-up	11.1% 1/9 • Number of events 1 • From randomization to 12-month follow-up
Gastrointestinal disorders Diarrhea	0.00% 0/11 • From randomization to 12-month follow-up	11.1% 1/9 • Number of events 1 • From randomization to 12-month follow-up
General disorders Headache	0.00% 0/11 • From randomization to 12-month follow-up	11.1% 1/9 • Number of events 1 • From randomization to 12-month follow-up

Additional Information

Penny Phillips

Ottawa Hospital Research Institute

Phone: 613-737-8899

Email: pphillips@ohri.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place