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

• Sponsor: Kirby Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02394730
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH), University of Minnesota (Other), University of Melbourne (Other), Merck Sharp & Dohme LLC (Industry)
• Enrollment: 65
• Locations: 7
• Arms: 2
• Duration (Months): 28
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

ADVICE is a randomised, international, double-blind, placebo-controlled trial. The purpose of the ADVICE study is to compare the safety and efficacy of vorapaxar in reducing d-dimer expression and markers of cellular immune activation over a period of 12 weeks among people with HIV infection who are successfully treated with combination antiretroviral therapy containing an HIV integrase inhibitor. A secondary objective of the study will be to demonstrate that following cessation of vorapaxar in patients with well controlled HIV replication there will be an increase in the levels of d-dimer over a 6 week period. 60 participants from 4 clinical sites in Australia and the USA will be recruited and followed for a minimum of 18 weeks.

Condition or Disease	Intervention/Treatment	Phase
HIV	Drug: vorapaxar; Drug: Placebo	Phase 1/Phase 2

Detailed Description

Consenting participants will be screened and within 14 days randomly allocated to receive either vorapaxar (2.5mg) or matched placebo once daily for 12 weeks (phase 1). Participants will be seen one week after randomisation and then at weeks 4, 8 and 12 (phase 1). At the week 12 visit, patients will not be dispensed any study treatment. In phase 2 all study treatment will stop for 6 weeks. At week 18 patients will be seen for a final study visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double Blind Randomised Comparison of Vorapaxar Versus Placebo for the Treatment of HIV Associated Inflammation and Coagulopathy in Patients With Well Controlled HIV Replication
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: vorapaxar 2.5mg of vorapaxar po qd	Drug: vorapaxar; 2.5mg of vorapaxar taken orally once daily for 12 weeks; Other Names: Zontivity
Placebo Comparator: Placebo sugar pill po qd	Drug: Placebo; Sugar pill taken orally once daily for 12 weeks; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Mean Percent Change From Baseline for D-dimer (ng/mL) to the Average of Weeks 8 and 12 [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.

Secondary Outcome Measures

1. Number of Participants in Each Treatment Group With Plasma HIV-1 RNA <50 Copies/mL [at week 18]

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

2. Mean Change From Baseline to Week 12 in CD4+ Cell Counts [at week 12]

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

3. Mean Change From Baseline to Week 12 in CD8+ Cell Counts [at week 12]

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

4. Number of Patients in Each Treatment Group With D-dimer <165ng/mL at Week 12 [week 12]

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

5. Number of Patients in Each Treatment Group With D-dimer > or Equal to 165ng/mL at Week 18 [week 18]

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

6. Mean Change From Baseline in log10 D-Dimer [at week 18]

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

7. Mean Change From Baseline in log10 Hs-CRP at Week 18 [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

8. Percent Change From Baseline Hs-CRP (ug/mL) to the Average of Week 8 and Week 12 [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.

9. Mean Percent Change From Baseline IL-6 (pg/mL) to the Average of Week 8 and Week 12 [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.

10. Differences Between Treatment Groups in Mean Change From Baseline log10 IL-6 [at week 18]

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

11. Total Number of Participants With BARC Type 1, 2, 3, 4, or 5 Bleeding Episodes [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 -

12. Total Number of Participants With Any SAE Between Baseline and Week 18 [week 18]

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

13. Total Number of Participants With Any AE Between Baseline to Week 18 [week 18]

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

14. Changes From Baseline in Renal Function Measured by the CKD-EPI Estimate of Creatinine Clearance at Week 12 [at week 12]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. HIV-1 positive by licensed diagnostic test

2. aged ≥40 years

3. plasma HIV RNA <50 copies/mL for at least 24 weeks

4. screening CD4+ cell count > 50 cells/mm3

5. treated for at least 12 weeks with a suppressive regimen of combination antiretroviral therapy that does not include HIV protease inhibitors and/or NNRTIs (except rilpivirine)

6. plasma d-dimer >200ng/mL (>0.2μg/mL or >0.2mg/L) fibrinogen equivalent units or

100ng/mL (>0.1 μg/mL or >0.1mg/L) d-dimer units in the absence of established cause (deep vein thrombosis/embolism)

1. provision of written informed consent

Exclusion Criteria:

1. Absolute neutrophil count (ANC) <1000 cells/μL

2. hemoglobin <10.0 g/dL

3. platelet count <75,000 cells/μL

4. AST and/or ALT >2.5 x ULN

5. estimated glomerular filtration rate <30mL/min/1.73m2 ) using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation

6. history of myocardial infarction or unstable atherosclerotic disease

7. history of ischemic stroke or transient ischaemic attack (TIA)

8. active peptic/duodenal ulcer or other bleeding disorder within the previous 12 months

9. intent to have surgery within the 6 month period after randomisation

10. current use of aspirin or P2Y12 antiplatelet therapy

11. use of anticoagulants, (eg. heparin or warfarin), fibrinolytic therapy, chronic use (more than 5 consecutive days) of nonsteroidal anti-inflammatory drugs (NSAIDS), strong CYP3A4 inhibitors or inducers. See Manual of Operations for full list of medications to avoid.

12. participants unlikely to be able to remain in follow-up

13. pregnant or nursing mothers

14. in the clinical judgement of the investigator, participation in this trial is deemed inappropriate as this may conflict with the well-being of the participant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgetown University Hospital	Georgetown	Maryland	United States	20007
2	Hennepin County Medical Centre	Minneapolis	Minnesota	United States	55415
3	St Vincent's Hospital	Darlinghurst	New South Wales	Australia	2010
4	Taylor Square Private Clinic	Darlinghurst	New South Wales	Australia	2010
5	Melbourne Sexual Health Centre	Carlton	Victoria	Australia	3053
6	Monash Medical Centre	Melbourne	Victoria	Australia	3168
7	Northside Clinic	North Fitzroy	Victoria	Australia	3068

Sponsors and Collaborators

• Kirby Institute
• National Institute of Allergy and Infectious Diseases (NIAID)
• University of Minnesota
• University of Melbourne
• Merck Sharp & Dohme LLC

Investigators

• Study Director: Sean Emery, University of NSW, Kirby Institute

Study Documents (Full-Text)

• Study Protocol - Jul 12, 2016
• Statistical Analysis Plan - Nov 13, 2017

More Information

Publications

None provided.

• Responsible Party: Kirby Institute
• ClinicalTrials.gov Identifier: NCT02394730
• Other Study ID Numbers: 2014-01-ADV; AI000585-26-288416
• First Posted: Mar 20, 2015
• Last Update Posted: Mar 6, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Kirby Institute: HIV, d-dimer, hs-CRP, activated T-lymphocytes
• Additional relevant MeSH terms: Vorapaxar

Study Results

Participant Flow

Recruitment Details	Participants were screened and randomised from 2 sites in USA and 5 sites in Australia.
Pre-assignment Detail	125 were screened and 60 were not randomised (55 ineligible, 4 lost to follow up and 1 withdrew consent prior to randomisation).

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

Baseline Characteristics

Arm/Group Title	Vorapaxar	Placebo	Total
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks	Total of all reporting groups
Overall Participants	33	31	64
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	53	52	52
Sex: Female, Male (Count of Participants)
Female	2 6.1%	3 9.7%	5 7.8%
Male	31 93.9%	28 90.3%	59 92.2%
Race/Ethnicity, Customized (Count of Participants)
White	25 75.8%	23 74.2%	48 75%
Asian	1 3%	2 6.5%	3 4.7%
Black	7 21.2%	5 16.1%	12 18.8%
Hispanic/Latino	0 0%	1 3.2%	1 1.6%
Region of Enrollment (participants) [Number]
United States	12 36.4%	10 32.3%	22 34.4%
Australia	21 63.6%	21 67.7%	42 65.6%
Total Cholesterol (mmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mmol/L]	4.6	4.7	4.7
HDL Cholesterol ((mmol/L)) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [(mmol/L)]	1.2	1.3	1.2
Systolic blood pressure ((mm Hg)) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [(mm Hg)]	125	127	126.5
Diastolic blood pressure ((mm Hg)) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [(mm Hg)]	77	80	78.5
Current smoker (Count of Participants)
Count of Participants [Participants]	9 27.3%	9 29%	18 28.1%
Framingham 10 yr CHD Risk Score (Percentage of risk) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Percentage of risk]	10.6	12.1	11.4
d-dimer (ng/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ng/mL]	432.5	391.6	421.9
High sensitivity C Reactive Protein (hs-CRP) (ug/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ug/mL]	1.53	1.97	1.58
Interleukin 6 (IL-6) (pg/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [pg/mL]	0.93	0.99	0.94
Estimated duration of HIV infection (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	12.8	12.2	12.5
Plasma HIV RNA (copies/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [copies/mL]	20	20	20
CD4 count (cells per uL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells per uL]	639	698	643
Time on current Anti-Retroviral Treatment regimen (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	1.3	2	1.5

Outcome Measures

1. Primary Outcome

Title	Mean Percent Change From Baseline for D-dimer (ng/mL) to the Average of Weeks 8 and 12
Description	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.
Time Frame	at week 8 and week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	31
Mean (95% Confidence Interval) [percent]	-10.8	-8.5

2. Secondary Outcome

Title	Number of Participants in Each Treatment Group With Plasma HIV-1 RNA <50 Copies/mL
Description	Number of participants in each treatment group with plasma HIV-1 RNA <50 copies/mL at week 18
Time Frame	at week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	30
Count of Participants [Participants]	31 93.9%	29 93.5%

3. Secondary Outcome

Title	Mean Change From Baseline to Week 12 in CD4+ Cell Counts
Description	Mean of week 12 CD4+ cell count minus mean of week 0 CD4+ cell count
Time Frame	at week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	29	28
Mean (Standard Deviation) [cells/mm3]	-21.3 (143.7)	-29.7 (400.3)

4. Secondary Outcome

Title	Mean Change From Baseline to Week 12 in CD8+ Cell Counts
Description	Mean of week 12 CD8+ cell count minus mean of week 0 CD4+ cell count
Time Frame	at week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	29	28
Mean (Standard Deviation) [cells/mm3]	3 (191.6)	81.1 (244.7)

5. Secondary Outcome

Title	Number of Patients in Each Treatment Group With D-dimer <165ng/mL at Week 12
Description	Number of patients in each treatment group with d-dimer <165ng/mL at week 12
Time Frame	week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	30
Count of Participants [Participants]	1 3%	2 6.5%

6. Secondary Outcome

Title	Number of Patients in Each Treatment Group With D-dimer > or Equal to 165ng/mL at Week 18
Description	Number of patients in each treatment group with d-dimer > or equal to 165ng/mL at week 18
Time Frame	week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	30
Count of Participants [Participants]	32 97%	29 93.5%

7. Secondary Outcome

Title	Mean Change From Baseline in log10 D-Dimer
Description	Differences between treatment groups in mean change from week 0 log10 d-dimer to week 18
Time Frame	at week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	30
Mean (95% Confidence Interval) [percent change]	-2.21	-14.1

8. Secondary Outcome

Title	Mean Change From Baseline in log10 Hs-CRP at Week 18
Description	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
Time Frame	at week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	30
Mean (Standard Deviation) [pg/mL]	-0.03 (0.39)	-0.10 (0.54)

9. Secondary Outcome

Title	Percent Change From Baseline Hs-CRP (ug/mL) to the Average of Week 8 and Week 12
Description	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.
Time Frame	week 8 and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	30
Mean (95% Confidence Interval) [Percent]	-0.02	-15.7

10. Secondary Outcome

Title	Mean Percent Change From Baseline IL-6 (pg/mL) to the Average of Week 8 and Week 12
Description	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.
Time Frame	at week 8 and week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	30
Mean (90% Confidence Interval) [percent]	12.6	-11.6

11. Secondary Outcome

Title	Differences Between Treatment Groups in Mean Change From Baseline log10 IL-6
Description	Differences between treatment groups in mean change from baseline log10 IL-6 at week 18
Time Frame	at week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	30
Mean (Standard Deviation) [pg/mL]	0.03 (0.36)	-0.10 (0.25)

12. Secondary Outcome

Title	Total Number of Participants With BARC Type 1, 2, 3, 4, or 5 Bleeding Episodes
Description	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 -
Time Frame	at week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	31
Count of Participants [Participants]	12 36.4%	10 32.3%

13. Secondary Outcome

Title	Total Number of Participants With Any SAE Between Baseline and Week 18
Description	Total number of participants with any SAE between baseline and week 18
Time Frame	week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	31
Count of Participants [Participants]	3 9.1%	2 6.5%

14. Secondary Outcome

Title	Total Number of Participants With Any AE Between Baseline to Week 18
Description	Total number of participants with any AE between week 0 to week 18
Time Frame	week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	33	31
Count of Participants [Participants]	28 84.8%	28 90.3%

15. Secondary Outcome

Title	Changes From Baseline in Renal Function Measured by the CKD-EPI Estimate of Creatinine Clearance at Week 12
Description	Changes from baseline in renal function measured by the CKD-EPI estimate of creatinine clearance at week 12
Time Frame	at week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorapaxar	Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks	sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
Measure Participants	31	30
Mean (Standard Deviation) [ml/min/1.73m2]	2.08 (8.38)	2.05 (7.71)

Adverse Events

Time Frame	18 weeks
Arm/Group Title	Vorapaxar		Placebo
Arm/Group Description	2.5mg of vorapaxar po qd vorapaxar: 2.5mg of vorapaxar taken orally once daily for 12 weeks		sugar pill po qd Placebo: Sugar pill taken orally once daily for 12 weeks
All Cause Mortality
	Vorapaxar		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/31 (0%)
Serious Adverse Events
	Vorapaxar		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/33 (6.1%)		2/31 (6.5%)
Gastrointestinal disorders
Colitis	0/33 (0%)	0	1/31 (3.2%)	1
Injury, poisoning and procedural complications
Post Procedural haematoma	1/33 (3%)	1	0/31 (0%)	0
Metabolism and nutrition disorders
Gout	1/33 (3%)	1	0/31 (0%)	0
Nervous system disorders
spinal stenosis	1/33 (3%)	1	0/31 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/33 (0%)	0	1/31 (3.2%)	1
Other (Not Including Serious) Adverse Events
	Vorapaxar		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/33 (45.5%)		22/31 (71%)
Blood and lymphatic system disorders
Epistaxis	4/33 (12.1%)	6	2/31 (6.5%)	2
Gastrointestinal disorders
Vomiting	0/33 (0%)	0	2/31 (6.5%)	2
Dyspepsia	2/33 (6.1%)	2	1/31 (3.2%)	1
General disorders
Chest pain	2/33 (6.1%)	2	1/31 (3.2%)	1
Peripheral Swelling	1/33 (3%)	1	2/31 (6.5%)	2
Injury, poisoning and procedural complications
Laceration	3/33 (9.1%)	3	3/31 (9.7%)	3
Metabolism and nutrition disorders
Gout	2/33 (6.1%)	5	0/31 (0%)	0
Musculoskeletal and connective tissue disorders
Contusion	1/33 (3%)	1	3/31 (9.7%)	3
Back pain	1/33 (3%)	1	2/31 (6.5%)	2
Pain in extremety	0/33 (0%)	0	2/31 (6.5%)	2
Nervous system disorders
Headache	4/33 (12.1%)	4	2/31 (6.5%)	2
Dizziness	0/33 (0%)	0	2/31 (6.5%)	2
Paraesthesia	0/33 (0%)	0	2/31 (6.5%)	2
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Injection	4/33 (12.1%)	4	7/31 (22.6%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.