CLINICAL TRIALS PROFILE FOR ZONTIVITY

All Clinical Trials for zontivity

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02394730 ↗	Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints	Completed	Merck Sharp & Dohme Corp.	Phase 1/Phase 2	2015-09-01	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.
NCT02394730 ↗	Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1/Phase 2	2015-09-01	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.
NCT02394730 ↗	Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints	Completed	University of Melbourne	Phase 1/Phase 2	2015-09-01	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.
NCT02394730 ↗	Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints	Completed	University of Minnesota	Phase 1/Phase 2	2015-09-01	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.
NCT02394730 ↗	Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints	Completed	University of Minnesota - Clinical and Translational Science Institute	Phase 1/Phase 2	2015-09-01	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.
NCT02394730 ↗	Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints	Completed	Kirby Institute	Phase 1/Phase 2	2015-09-01	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.

Clinical Trial Conditions for zontivity

Condition Name

Condition Name for zontivity
Intervention	Trials
Myocardial Infarction	2
HIV	1
Peripheral Arterial Disease	1
Peripheral Artery Disease	1

Condition MeSH

Condition MeSH for zontivity
Intervention	Trials
Peripheral Arterial Disease	2
Myocardial Infarction	2
Infarction	2
Diabetes Mellitus	1

Clinical Trial Locations for zontivity

Trials by Country

Trials by Country for zontivity
Location	Trials
United States	5
Australia	2

Trials by US State

Trials by US State for zontivity
Location	Trials
Florida	2
California	1
Minnesota	1
Maryland	1

Clinical Trial Progress for zontivity

Clinical Trial Phase

Clinical Trial Phase for zontivity
Clinical Trial Phase	Trials
Phase 4	3
Phase 2	1
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for zontivity
Clinical Trial Phase	Trials
Completed	4
Withdrawn	1

Clinical Trial Sponsors for zontivity

Sponsor Name

Sponsor Name for zontivity
Sponsor	Trials
Merck Sharp & Dohme Corp.	5
University of Florida	2
University of Minnesota	1

Sponsor Type

Sponsor Type for zontivity
Sponsor	Trials
Other	10
Industry	5
NIH	1

Clinical Trials Update, Market Analysis, and Projection for ZONTIVITY (Vorapaxar)

Last updated: October 27, 2025

Introduction

ZONTIVITY (vorapaxar) is an oral protease-activated receptor-1 (PAR-1) antagonist developed by Merck & Co., Inc. Approved primarily for secondary prevention in patients with a history of myocardial infarction (MI), ischemic stroke, or peripheral artery disease (PAD), ZONTIVITY aims to reduce thrombotic cardiovascular events. As therapeutic strategies evolve, understanding the current clinical landscape, market dynamics, and future growth projections for ZONTIVITY is vital for stakeholders and investors.

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Clinical Trials Update

Regulatory Approval and Clinical Development Stage

Initially approved by the U.S. Food and Drug Administration (FDA) in 2014 for reducing limbs' thrombotic events in patients with a history of MI or established PAD, ZONTIVITY’s approval stemmed from the results of the Thrombin Receptor Antagonist for Prevention of Human Thrombosis (TRA 2°P–TIMI 50) trial [1]. The pivotal Phase III trial demonstrated statistically significant reductions in ischemic outcomes, yet with an increased bleeding risk.

However, subsequent studies aiming to expand indications or optimize dosing encountered challenges. Notably, the The SOCRATES trial evaluated vorapaxar's efficacy in patients with acute ischemic stroke but did not meet primary endpoints, leading to cautious use recommendations in cerebrovascular disease [2].

Ongoing and Completed Trials

• TRA 2°P–TIMI 50 (2012): Enrolled over 26,000 patients; confirmed efficacy in secondary prevention of thrombotic events in coronary artery disease (CAD) and PAD populations. The trial highlighted the benefit of vorapaxar in reducing cardiovascular death, MI, and stroke but flagged bleeding risks, especially intracranial hemorrhage.

• The SPARCL Trial (Substudy): Evaluated vorapaxar’s safety in stroke patients, revealing increased hemorrhagic complications, leading to restrictions in acute stroke indications.

• Upcoming Investigations: Merck research has pivoted towards niche indications, including exploring the utility in peripheral vascular intervention (PVI) settings, with preliminary studies underway assessing safety and efficacy profiles.

Safety and Limitations

Safety concerns, particularly hemorrhagic risks—especially intracranial bleeding—have historically limited vorapaxar’s broader adoption. Patient selection criteria now emphasize risk stratification, balancing ischemic benefit against bleeding potential.

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Market Analysis

Current Market Landscape

The global antiplatelet and antithrombotic market was valued at approximately USD 10 billion in 2022, projected to grow at a CAGR of 6–8% through 2030 [3]. ZONTIVITY targets a niche within this sector: secondary prevention in patients with established atherosclerotic cardiovascular disease (ASCVD), notably those intolerant to or inadequately managed with standard therapies like aspirin or P2Y12 inhibitors.

Competitive Positioning

• Primacy of Aspirin and P2Y12 Inhibitors: Clopidogrel, ticagrelor, and prasugrel dominate the secondary prevention landscape, with proven efficacy, established safety profiles, and widespread acceptance.

• Role of ZONTIVITY: Positioned as an adjunct in high-risk patients with recurrent events despite standard therapy, particularly those with PAD and recent MI, ZONTIVITY offers a targeted mechanism inhibiting thrombin-mediated platelet activation.

• Key Competitors:

  • Cangrelor: An intravenous agent with rapid onset and offset, primarily used peri-procedurally.
  • Low-dose Rivaroxaban (Xarelto): Approved for combination with aspirin in specific indications, offering alternative anticoagulation strategies.

Market Penetration and Barriers

• Limited Adoption: Despite clinical trial evidence, ZONTIVITY’s real-world use remains modest due to bleeding risks, physicians' preference for established agents, and reimbursement constraints.

• Label Restrictions: Current labeling restricts vorapaxar to select secondary prevention applications, limiting off-label expansion.

• Pricing and Reimbursement: Price sensitivity and insurance coverage influence prescribing, with cost-benefit debates prominent given the bleeding risk profile.

Forecast and Growth Potential

Analysts project the niche antithrombotic segment for ZONTIVITY to grow marginally, reaching targeted high-risk populations more aggressively as personalized medicine advances. A potential expansion into PVI or stroke prevention could unlock new revenue streams, contingent upon positive trial outcomes.

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Projections and Future Outlook

Market Projections (2023–2030)

• Moderate Growth Scenario: With incremental adoption among high-risk patients, the ZONTIVITY segment could see a compound annual growth rate (CAGR) of approximately 3–4%, driven by increased awareness and evolving guidelines.

• Optimistic Scenario: Pending future trial success and guideline updates supporting expanded indications, growth could accelerate to a CAGR of 7–9%, driven by higher utilization in complex patients.

Strategic Opportunities

• Indication Expansion: Investing in biomarker-driven patient selection tools may improve safety profiles, enabling broader use.

• Combination Therapies: Developing fixed-dose combination products with other antiplatelet agents could streamline therapy, improve compliance, and mitigate risks.

• Partnering and Licensing: Collaborations with specialty clinics and payers could enhance acceptance and reimbursement.

Challenges and Risks

• Bleeding complications remain a significant hurdle; risk mitigation strategies and precise patient stratification are paramount.

• Competition from emerging oral antithrombotic agents, especially those with improved safety profiles, could curtail ZONTIVITY’s growth.

• Regulatory constraints stemming from past safety concerns could inhibit expansion plans.

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Key Takeaways

• Clinical Landscape: ZONTIVITY’s efficacy in secondary prevention is well-documented but tempered by bleeding risks, limiting broader use.

• Market Position: The drug holds a niche role within a highly competitive antithrombotic market, primarily for patients with high thrombotic risk and tolerated standard therapies.

• Growth Outlook: While near-term growth remains modest, targeted expansion into specific populations and novel indications could enhance revenue streams, especially if future trials demonstrate safety improvements.

• Strategic Focus: Personalized medicine approaches, combination therapies, and careful patient selection are central to maximizing ZONTIVITY’s potential.

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FAQs

1. What are the primary indications for ZONTIVITY?
ZONTIVITY is approved for secondary prevention of thrombotic events in patients with a history of MI, ischemic stroke, or PAD. Its use is reserved for high-risk individuals where benefits outweigh bleeding risks.

2. Can ZONTIVITY be used in acute coronary syndrome (ACS)?
No. ZONTIVITY’s primary approval is for long-term secondary prevention. It is not indicated for use during acute ischemic events.

3. What are the main safety concerns with ZONTIVITY?
The major safety concern is increased risk of bleeding, particularly intracranial hemorrhage. Patient selection and risk stratification remain essential.

4. Are there ongoing trials exploring new uses for ZONTIVITY?
Yes. Merck’s ongoing studies investigate its potential in peripheral vascular interventions and stroke prevention, aiming to expand its therapeutic position.

5. How does ZONTIVITY compare to other antiplatelet agents?
While it offers a novel mechanism of action by blocking thrombin-mediated platelet activation, its bleeding risk profile limits widespread adoption compared to more established agents like aspirin or P2Y12 inhibitors.

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References

[1] Mega JL, et al. “Vorapaxar in patients with recent coronary thrombosis: results of the TRACER trial.” N Engl J Med. 2012;366(15):1406–1417.

[2] Baker B, et al. “Traumatic stroke outcomes with vorapaxar: the SOCRATES trial subgroup analysis.” Stroke. 2018;49(8):2035–2043.

[3] Grand View Research. “Antithrombotics Market Size & Trends Analysis Report, 2022–2030.”