Vorapaxar as an Add-On Antiplatelet Therapy in Patients With and Without Diabetes Mellitus (OPTIMUS-5)

• ClinicalTrials.gov Identifier: NCT02548650
• Recruitment Status: Completed
• First Posted: September 14, 2015
• Results First Posted: January 27, 2020
• Last Update Posted: February 12, 2020
• Sponsor: University of Florida
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): University of Florida

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Myocardial Infarction; Diabetes Mellitus; Peripheral Arterial Disease
• Interventions: Drug: Vorapaxar; Drug: Clopidogrel; Drug: Aspirin
• Enrollment: 66

Participant Flow

Recruitment Details
Pre-assignment Details	Between March 2016 and October 2018, 71 patients agreed to participate in the study; 5 patients were not eligible for randomization due to the presence of an exclusion criteria. 66 patients (DM, n=30; non-DM, n=36) were exposed to at least one dose of study medication, representing the safety population.

Arm/Group Title	Patients With Diabetes	Patients Without Diabetes
Arm/Group Description	Triple therapy (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days.	Triple therapy (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days.
Period Title: Triple Therapy
Started	30	36
Completed	29	32
Not Completed	1	4
Reason Not Completed
Adverse Event	1	0
Withdrawal by Subject	0	4
Period Title: Double Therapy
Started	29	32
Completed	28	30
Not Completed	1	2
Reason Not Completed
Adverse Event	1	1
Withdrawal by Subject	0	1

Baseline Characteristics

Arm/Group Title		Patients With Diabetes	Patients Without Diabetes	Total
Arm/Group Description		Triple therapy (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days.	Triple therapy (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days.	Total of all reporting groups
Overall Number of Baseline Participants		30	34	64
Baseline Analysis Population Description		Two patients were not compliant with medications and therefore excluded from the PD analysis. Thus, a total of 64 patients (DM, n=30; non-DM, n=34) represented the PD population of the study and were analyzed for baseline characteristics and PD data.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	30 participants	34 participants	64 participants
		61 (8)	56 (9)	58 (10)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	34 participants	64 participants
	Female	7 23.3%	11 32.4%	18 28.1%
	Male	23 76.7%	23 67.6%	46 71.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	34 participants	64 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	14 46.7%	11 32.4%	25 39.1%
	White	15 50.0%	22 64.7%	37 57.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 3.3%	1 2.9%	2 3.1%
chronic kidney disease; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	34 participants	64 participants
		2 6.7%	2 5.9%	4 6.3%

Outcome Measures

1. Primary Outcome

Title	Maximal Platelet Aggregation in DM
Description	Comparison of maximal platelet aggregation (%) measured by light transmittance aggregometry between between triple (vorapaxar plus DAPT) and dual (vorapaxar plus clopidogrel) therapy in diabetic patients
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

The PD population included all patients with PD data and without a major protocol deviation thought to affect the PD effects of vorapaxar, aspirin and clopidogrel. Two patients were not compliant with medications and therefore excluded from the PD analysis. Some patients did not have primary end point data but were considered for other analyses.

Arm/Group Title	Triple Therapy	Dual Therapy
Arm/Group Description:	vorapaxar plus DAPT	(vorapaxar plus clopidogrel)
Overall Number of Participants Analyzed	30	30
Mean (Standard Deviation); Unit of Measure: percentage of aggregation
	65 (20)	78 (20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Triple Therapy, Dual Therapy
	Comments	The primary end point of our study was the comparison of CAT-induced MPA measured by LTA between triple (vorapaxar plus DAPT) and dual (vorapaxar plus clopidogrel) therapy. We hypothesized that dual therapy would be non-inferior to triple therapy after 30±5 days of treatment
	Type of Statistical Test	Non-Inferiority
	Comments	Under the null hypothesis that the mean aggregation between dual and triple therapy is not equal to 0 and a common standard deviation of 13%, a sample size of 28 patients per group with a valid primary end point time point allowed for the 95% confidence interval (CI) to stay within ± 10% with a 80% power and a two-sided alpha=0.05.
Statistical Test of Hypothesis	P-Value	>0.05
	Comments	[Not Specified]
	Method	ANOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	12
	Confidence Interval	(2-Sided) 95%; 3 to 21
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Maximal Platelet Aggregation in Non-DM
Description	Comparison of maximal platelet aggregation (%) measured by light transmittance aggregometry between between triple (vorapaxar plus DAPT) and dual (vorapaxar plus clopidogrel) therapy in non-diabetic patients
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Triple Therapy	Dual Therapy
Arm/Group Description:	vorapaxar plus DAPT	(vorapaxar plus clopidogrel)
Overall Number of Participants Analyzed	34	34
Mean (Standard Deviation); Unit of Measure: percentage of aggregation
	60 (15)	70 (20)

Adverse Events

Time Frame	Study duration (60 days)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Patients With Diabetes		Patients Without Diabetes
Arm/Group Description	Triple therapy (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days.		Triple therapy (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days.
All-Cause Mortality
	Patients With Diabetes		Patients Without Diabetes
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/30 (0.00%)		0/36 (0.00%)
Serious Adverse Events
	Patients With Diabetes		Patients Without Diabetes
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0.00%)		0/36 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Patients With Diabetes		Patients Without Diabetes
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/30 (6.67%)		2/36 (5.56%)
Blood and lymphatic system disorders
minor bleeding * [1]	1/30 (3.33%)	1	0/36 (0.00%)	0
Cardiac disorders
Chest pain * [2]	1/30 (3.33%)	1	2/36 (5.56%)	2
* Indicates events were collected by non-systematic assessment; [1] hematuria; [2] chest pain not requiring intervention

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dominick J Angiolillo
• Organization: University of Florida College of Medicine - Jacksonville
• Phone: 9042443933
• EMail: dominick.angiolillo@jax.ufl.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Franchi F, Rollini F, Kairouz V, Rivas Rios J, Rivas A, Agarwal M, Briceno M, Wali M, Nawaz A, Silva G, Shaikh Z, Maaliki N, Been L, Piraino J, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Jennings LK, Bass TA, Angiolillo DJ. Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus: Results of the OPTIMUS-5 Study. JACC Basic Transl Sci. 2019 Sep 1;4(7):763-775. doi: 10.1016/j.jacbts.2019.07.011. eCollection 2019 Nov.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02548650
• Other Study ID Numbers: IIS 53377
• First Submitted: September 8, 2015
• First Posted: September 14, 2015
• Results First Submitted: January 10, 2020
• Results First Posted: January 27, 2020
• Last Update Posted: February 12, 2020