Trial Outcomes & Findings for Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints (NCT NCT02394730)

NCT ID: NCT02394730

Last Updated: 2019-03-06

Results Overview

Mean of week 8 and week 12 minus week 0 (on log10 scale) then back transforming the log10 difference to obtain percentage change from baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 65 participants
• Primary outcome timeframe: at week 8 and week 12
• Results posted on: 2019-03-06

Participant Flow

Participants were screened and randomised from 2 sites in USA and 5 sites in Australia.

125 were screened and 60 were not randomised (55 ineligible, 4 lost to follow up and 1 withdrew consent prior to randomisation).

Participant milestones

Measure	Vorapaxar 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Overall Study STARTED	34	31
Overall Study COMPLETED	33	30
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Vorapaxar 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints

Baseline characteristics by cohort

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=31 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks	Total n=64 Participants Total of all reporting groups
Age, Continuous	53 years n=5 Participants	52 years n=7 Participants	52 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	28 Participants n=7 Participants	59 Participants n=5 Participants
Race/Ethnicity, Customized White	25 Participants n=5 Participants	23 Participants n=7 Participants	48 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Black	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	10 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Australia	21 participants n=5 Participants	21 participants n=7 Participants	42 participants n=5 Participants
Total Cholesterol	4.6 mmol/L n=5 Participants	4.7 mmol/L n=7 Participants	4.7 mmol/L n=5 Participants
HDL Cholesterol	1.2 (mmol/L) n=5 Participants	1.3 (mmol/L) n=7 Participants	1.2 (mmol/L) n=5 Participants
Systolic blood pressure	125 (mm Hg) n=5 Participants	127 (mm Hg) n=7 Participants	126.5 (mm Hg) n=5 Participants
Diastolic blood pressure	77 (mm Hg) n=5 Participants	80 (mm Hg) n=7 Participants	78.5 (mm Hg) n=5 Participants
Current smoker	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Framingham 10 yr CHD Risk Score	10.6 Percentage of risk n=5 Participants	12.1 Percentage of risk n=7 Participants	11.4 Percentage of risk n=5 Participants
d-dimer	432.5 ng/mL n=5 Participants	391.6 ng/mL n=7 Participants	421.9 ng/mL n=5 Participants
High sensitivity C Reactive Protein (hs-CRP)	1.53 ug/mL n=5 Participants	1.97 ug/mL n=7 Participants	1.58 ug/mL n=5 Participants
Interleukin 6 (IL-6)	0.93 pg/mL n=5 Participants	0.99 pg/mL n=7 Participants	0.94 pg/mL n=5 Participants
Estimated duration of HIV infection	12.8 years n=5 Participants	12.2 years n=7 Participants	12.5 years n=5 Participants
Plasma HIV RNA	20 copies/mL n=5 Participants	20 copies/mL n=7 Participants	20 copies/mL n=5 Participants
CD4 count	639 cells per uL n=5 Participants	698 cells per uL n=7 Participants	643 cells per uL n=5 Participants
Time on current Anti-Retroviral Treatment regimen	1.3 years n=5 Participants	2 years n=7 Participants	1.5 years n=5 Participants

PRIMARY outcome

Timeframe: at week 8 and week 12

Mean of week 8 and week 12 minus week 0 (on log10 scale) then back transforming the log10 difference to obtain percentage change from baseline.

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=31 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Mean Percent Change From Baseline for D-dimer (ng/mL) to the Average of Weeks 8 and 12	-10.8 percent Interval -23.1 to 3.4	-8.5 percent Interval -18.4 to 2.5

SECONDARY outcome

Timeframe: at week 18

Number of participants in each treatment group with plasma HIV-1 RNA <50 copies/mL at week 18

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=30 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Number of Participants in Each Treatment Group With Plasma HIV-1 RNA <50 Copies/mL	31 Participants	29 Participants

SECONDARY outcome

Timeframe: at week 12

Mean of week 12 CD4+ cell count minus mean of week 0 CD4+ cell count

Outcome measures

Measure	Vorapaxar n=29 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=28 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Mean Change From Baseline to Week 12 in CD4+ Cell Counts	-21.3 cells/mm3 Standard Deviation 143.7	-29.7 cells/mm3 Standard Deviation 400.3

SECONDARY outcome

Timeframe: at week 12

Mean of week 12 CD8+ cell count minus mean of week 0 CD4+ cell count

Outcome measures

Measure	Vorapaxar n=29 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=28 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Mean Change From Baseline to Week 12 in CD8+ Cell Counts	3 cells/mm3 Standard Deviation 191.6	81.1 cells/mm3 Standard Deviation 244.7

SECONDARY outcome

Timeframe: week 12

Number of patients in each treatment group with d-dimer <165ng/mL at week 12

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=30 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Number of Patients in Each Treatment Group With D-dimer <165ng/mL at Week 12	1 Participants	2 Participants

SECONDARY outcome

Timeframe: week 18

Number of patients in each treatment group with d-dimer > or equal to 165ng/mL at week 18

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=30 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Number of Patients in Each Treatment Group With D-dimer > or Equal to 165ng/mL at Week 18	32 Participants	29 Participants

SECONDARY outcome

Timeframe: at week 18

Differences between treatment groups in mean change from week 0 log10 d-dimer to week 18

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=30 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Mean Change From Baseline in log10 D-Dimer	-2.21 percent change Interval -17.9 to 16.5	-14.1 percent change Interval -17.7 to 17.9

SECONDARY outcome

Timeframe: at week 18

Differences between treatment groups in mean change from baseline log10 hs-CRP to week 18. ie Week 18 log10 hs-CRP minus week 0 log10 hs-CRP

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=30 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Mean Change From Baseline in log10 Hs-CRP at Week 18	-0.03 pg/mL Standard Deviation 0.39	-0.10 pg/mL Standard Deviation 0.54

SECONDARY outcome

Timeframe: week 8 and 12

Mean of week 8 and week 12 minus week 0 (on log10 scale) then back transformed the log10 difference to obtain percentage change from baseline.

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=30 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Percent Change From Baseline Hs-CRP (ug/mL) to the Average of Week 8 and Week 12	-0.02 Percent Interval -41.3 to 70.2	-15.7 Percent Interval -40.9 to 20.2

SECONDARY outcome

Timeframe: at week 8 and week 12

Mean of week 8 and week 12 minus week 0 (on log10 scale) then back transformed the log10 difference to obtain percentage change from baseline.

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=30 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Mean Percent Change From Baseline IL-6 (pg/mL) to the Average of Week 8 and Week 12	12.6 percent Interval -15.6 to 50.4	-11.6 percent Interval -29.1 to 10.3

SECONDARY outcome

Timeframe: at week 18

Differences between treatment groups in mean change from baseline log10 IL-6 at week 18

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=30 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Differences Between Treatment Groups in Mean Change From Baseline log10 IL-6	0.03 pg/mL Standard Deviation 0.36	-0.10 pg/mL Standard Deviation 0.25

SECONDARY outcome

Timeframe: at week 18

Bleeding Academic Research Consortium (BARC) Definitions for Bleeding Events Type 1 -bleeding that is not actionable and does not cause the patient to seek unscheduled performance of studies, hospitalization, or treatment by a healthcare professional; may include episodes leading to self-discontinuation of medical therapy by the patient without consulting a healthcare professional Type 2 - overt, actionable sign of haemorrhage (eg, more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for type 3, 4, or 5 but does meet at least one of the following criteria: (1) requiring nonsurgical, medical intervention by a healthcare professional, (2) leading to hospitalization or increased level of care, or (3) prompting evaluation Type 3- Bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid) Type 4 - Coronary Artery Bypass Graft procedure-related bleeding Type 5 -

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=31 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Total Number of Participants With BARC Type 1, 2, 3, 4, or 5 Bleeding Episodes	12 Participants	10 Participants

SECONDARY outcome

Timeframe: week 18

Total number of participants with any SAE between baseline and week 18

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=31 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Total Number of Participants With Any SAE Between Baseline and Week 18	3 Participants	2 Participants

SECONDARY outcome

Timeframe: week 18

Total number of participants with any AE between week 0 to week 18

Outcome measures

Measure	Vorapaxar n=33 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=31 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Total Number of Participants With Any AE Between Baseline to Week 18	28 Participants	28 Participants

SECONDARY outcome

Timeframe: at week 12

Changes from baseline in renal function measured by the CKD-EPI estimate of creatinine clearance at week 12

Outcome measures

Measure	Vorapaxar n=31 Participants 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=30 Participants sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Changes From Baseline in Renal Function Measured by the CKD-EPI Estimate of Creatinine Clearance at Week 12	2.08 ml/min/1.73m2 Standard Deviation 8.38	2.05 ml/min/1.73m2 Standard Deviation 7.71

Adverse Events

Vorapaxar

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vorapaxar n=33 participants at risk 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=31 participants at risk sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/33 • 18 weeks	3.2% 1/31 • Number of events 1 • 18 weeks
Gastrointestinal disorders Colitis	0.00% 0/33 • 18 weeks	3.2% 1/31 • Number of events 1 • 18 weeks
Nervous system disorders spinal stenosis	3.0% 1/33 • Number of events 1 • 18 weeks	0.00% 0/31 • 18 weeks
Injury, poisoning and procedural complications Post Procedural haematoma	3.0% 1/33 • Number of events 1 • 18 weeks	0.00% 0/31 • 18 weeks
Metabolism and nutrition disorders Gout	3.0% 1/33 • Number of events 1 • 18 weeks	0.00% 0/31 • 18 weeks

Other adverse events

Measure	Vorapaxar n=33 participants at risk 2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	Placebo n=31 participants at risk sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Injection	12.1% 4/33 • Number of events 4 • 18 weeks	22.6% 7/31 • Number of events 8 • 18 weeks
Injury, poisoning and procedural complications Laceration	9.1% 3/33 • Number of events 3 • 18 weeks	9.7% 3/31 • Number of events 3 • 18 weeks
Blood and lymphatic system disorders Epistaxis	12.1% 4/33 • Number of events 6 • 18 weeks	6.5% 2/31 • Number of events 2 • 18 weeks
Nervous system disorders Headache	12.1% 4/33 • Number of events 4 • 18 weeks	6.5% 2/31 • Number of events 2 • 18 weeks
Musculoskeletal and connective tissue disorders Contusion	3.0% 1/33 • Number of events 1 • 18 weeks	9.7% 3/31 • Number of events 3 • 18 weeks
General disorders Chest pain	6.1% 2/33 • Number of events 2 • 18 weeks	3.2% 1/31 • Number of events 1 • 18 weeks
Musculoskeletal and connective tissue disorders Back pain	3.0% 1/33 • Number of events 1 • 18 weeks	6.5% 2/31 • Number of events 2 • 18 weeks
Nervous system disorders Dizziness	0.00% 0/33 • 18 weeks	6.5% 2/31 • Number of events 2 • 18 weeks
Musculoskeletal and connective tissue disorders Pain in extremety	0.00% 0/33 • 18 weeks	6.5% 2/31 • Number of events 2 • 18 weeks
Nervous system disorders Paraesthesia	0.00% 0/33 • 18 weeks	6.5% 2/31 • Number of events 2 • 18 weeks
Gastrointestinal disorders Vomiting	0.00% 0/33 • 18 weeks	6.5% 2/31 • Number of events 2 • 18 weeks
General disorders Peripheral Swelling	3.0% 1/33 • Number of events 1 • 18 weeks	6.5% 2/31 • Number of events 2 • 18 weeks
Gastrointestinal disorders Dyspepsia	6.1% 2/33 • Number of events 2 • 18 weeks	3.2% 1/31 • Number of events 1 • 18 weeks
Metabolism and nutrition disorders Gout	6.1% 2/33 • Number of events 5 • 18 weeks	0.00% 0/31 • 18 weeks

Additional Information

Sean Emery, Chief Principal Investigator

University of New South Wales

Phone: +61 2 9385 0897

Email: s.emery@unsw.edu.au

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators need to submit a proposal, abstract, manuscript or other form of communication of trial results to the Protocol Steering Committee for review and approval.
• Publication restrictions are in place

Restriction type: OTHER