1-month DAPT Plus 5-month Ticagrelor Monotherapy Versus 12-month DAPT in Patients With Drug-coated Balloon (CAGEFREEII)

Aspirin Plus Ticagrelor for 1 Month Followed by 5 Months Ticagrelor Monotherapy Versus Aspirin Plus Ticagrelor for 12 Months in Acute Coronary Syndrome Patients With Drug-coated Balloon: a Multicentre, Randomized, Non-inferiority Trial

Drug-Coated Balloon (DCB) angioplasty is similar to plain old balloon angioplasty procedurally, but there is an anti-proliferative medication paclitaxel coated to the balloon. Treating ISR lesions with the DCB has the theoretical advantage of avoiding multiple stent layers and respecting the vessel anatomy. DCB has shown promising results for the treatment of ISR. Currently, DCB has a Class I indication to treat ISR recommended by European Society of Cardiology guidelines. In addition, some interventional cardiologist has also applied DCB in de novo lesions in their clinical practice.

Bleeding after PCI remains a substantial clinical problem. Bleeding post-PCI increases the risk of adverse outcomes such as death, non-fatal myocardial infarction, and prolongs hospital stay. Clinical data has suggested that major bleeding post-PCI would increase the risk of mortality 5.7-fold. The antiplatelet medications are the major cause of bleeding events post-PCI.

Current guidelines for stents recommended DAPT of aspirin plus a P2Y12 inhibitor for at least 12 months after stent implantation in patients with the acute coronary syndrome. Compared with the DES, because of the absence of metal inside the coronary artery, the use of DCB might theoretically allow shorter duration antiplatelet therapy. However, the optimal course of DAPT for the DCB treated patients remains controversial.

In 2013, the consensus from the German group suggested that for the acute coronary syndrome, DAPT should be used for 12 months. The consensus of DAPT developed by the European Society of Cardiology (ESC) in 2017 stated that "in patients treated with DCB, dedicated clinical trials investigating the optimal duration of DAPT are lacking." So far, there are no randomized data showing the optimal DAPT duration for the DCB treated patients.

In the current study, we use Aspirin + Ticagrelor for 1-month followed by Ticagrelor monotherapy for 5-month, afterward, Aspirin monotherapy for 6 months to be the antiplatelet regimen in the experimental arm, to compare with the Reference arm, which is Aspirin + Ticagrelor for 12-month in a non-inferiority statistical assumption, aiming to investigate the optimal duration of the DAPT in ACS patients after DCB treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Coronary Syndrome; Angioplasty, Balloon; Antiplatelet Drug
• Intervention / Treatment: Drug: Aspirin 100mg for 1-month (immediately after PCI); Drug: Ticagrelor 90mg for 6-month (immediately after PCI); Drug: Aspirin 100mg for 6-month (6-month post PCI); Drug: Aspirin 100mg for 12-month (immediately after PCI); Drug: Ticagrelor 90mg for 12-month (immediately after PCI)

• Study Type: Interventional
• Enrollment (Actual): 1948
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shannxi
    • Xi'an, Shannxi, China, 710032
      • Ling Tao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with an indication for PCI due to acute coronary syndrome
2. All target lesions can be successful treatment of PCI with drug-coated balloon (DCB)
3. Patients who are able to complete the follow-up and compliant to the prescribed medication

Exclusion Criteria:

1. Under the age of 18 or Older than 80 years old
2. Unable to give informed consent
3. Patient is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential according to local practice)
4. Known contraindication to medications such as Heparin, antiplatelet drugs, or contrast.
5. Currently participating in another trial and not yet at its primary endpoint
6. Planned elective surgery
7. Concurrent medical condition with a life expectancy of less than 1 years
8. Previous intracranial haemorrhage
9. Need long-term oral anticoagulant therapy
10. Cardiogenic shock
11. Previous stent implantation 6 month
12. In-stent thrombosis
13. Target lesion located in surgical conduit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm; 1-month of Aspirin + Ticagrelor, followed by 5-month of Ticagrelor monotherapy; Afterward, Aspirin monotherapy for 6 months	Drug: Aspirin 100mg for 1-month (immediately after PCI); Aspirin for 1-month immediately after PCI to be a part of medication treatment in the Experimental arm; Drug: Ticagrelor 90mg for 6-month (immediately after PCI); Ticagrelor for 6-month immediately after PCI to be a part of medication treatment in the Experimental arm; Drug: Aspirin 100mg for 6-month (6-month post PCI); Aspirin for 6-month at 6 months post-PCI (after the discontinuation of the 6-month Ticagrelor treatment) to be a part of medication treatment in the Experimental arm
Active Comparator: Reference arm; 12-month Aspirin plus Ticagrelor	Drug: Aspirin 100mg for 12-month (immediately after PCI); Aspirin for 12-month immediately after PCI to be a part of medication treatment in the Reference arm; Drug: Ticagrelor 90mg for 12-month (immediately after PCI); Ticagrelor for 12-month immediately after PCI to be a part of medication treatment in the Reference arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net adverse clinical events (NACE)	NACE is a composite clinical endpoint of all-cause death, any stroke, any MI, any revascularization and BARC type 3 or 5 bleeding events	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BARC type 3 or 5 bleeding events	Bleeding events type 3 or 5 defined by BARC (Bleeding Academic Research Consortium) criteria	1, 6 and 12 months
BARC type 2 ,3 or 5 bleeding events	Bleeding events type 2, 3 or 5 defined by BARC (Bleeding Academic Research Consortium) criteria	1, 6 and 12 months
BARC defined type 2 bleeding events	Bleeding events type 2 defined by BARC (Bleeding Academic Research Consortium) criteria	1, 6 and 12 months
Rate of NACE	NACE is a composite clinical endpoint of all-cause death, any stroke, any MI, any revascularization and BARC type 3 or 5 bleeding events	1 and 6 months
Device-oriented Composite Endpoint (DoCE)	DoCE is a composite clinical endpoint of cardiac cause death, target vessel myocardial infraction (TV-MI), and Clinically individual target lesion revascularization (CI-TLR)	1, 6 and 12 months
Cardiac death	Rates of individual components of DoCE	1, 6 and 12 months
Target vessel myocardial infraction (TV-MI)	Rates of individual components of DoCE	1, 6 and 12 months
Clinically individual target lesion revascularization (CI-TLR)	Rates of individual components of DoCE	1, 6 and 12 months
All-cause death	Rates of individual components of PoCE	1, 6 and 12 months
Any MI	Rates of individual components of PoCE	1, 6 and 12 months
Any stroke	Rates of individual components of PoCE	1, 6 and 12 months
Any revascularization	Rates of individual components of PoCE	1, 6 and 12 months
Target vessel failure (TVF)	Target vessel failure is defined as cardiovascular death, target vessel myocardial infraction (TV-MI), and clinically-indicated target vessel revascularization	1, 6 and 12 months
Clinically-indicated target vessel revascularization	Rates of individual components of TVF	1, 6 and 12 months
Definite/Probable stent thrombosis rates		1, 6 and 12 months
Any ischemic or bleeding event	Any ischemic and bleeding event includes any all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization and BARC-defined type 2 bleeding events	1, 6 and 12 months
Patient-oriented Composite Endpoint (PoCE)	The primary safety endpoint of PoCE is defined as all-cause death, any stroke, any MI, any revascularization	1, 6 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
BARC type 3 or 5 bleeding events	Bleeding events type 3 or 5 defined by BARC (Bleeding Academic Research Consortium) criteria	1 and 12 months
BARC type 2 ,3 or 5 bleeding events	Bleeding events type 2, 3 or 5 defined by BARC (Bleeding Academic Research Consortium) criteria	1 and 12 months
BARC defined type 2 bleeding events	Bleeding events type 2 defined by BARC (Bleeding Academic Research Consortium) criteria	1 and 12 months
Rate of NACE	NACE is a composite clinical endpoint of all-cause death, any stroke, any MI, any revascularization and BARC type 3 or 5 bleeding events	1 months
Device-oriented Composite Endpoint (DoCE)	DoCE is a composite clinical endpoint of cardiac cause death, target vessel myocardial infraction (TV-MI), and Clinically individual target lesion revascularization (CI-TLR)	1 and 12 months
Cardiac death	Rates of individual components of DoCE	1 and 12 months
Target vessel myocardial infraction (TV-MI)	Rates of individual components of DoCE	1 and 12 months
Clinically individual target lesion revascularization (CI-TLR)	Rates of individual components of DoCE	1 and 12 months
Patient-oriented Composite Endpoint (PoCE)	PoCE defined as all-cause death, any stroke, any MI, any revascularization	1 and 12 months
All-cause death	Rates of individual components of PoCE	1 and 12 months
Any MI	Rates of individual components of PoCE	1 and 12 months
Any stroke	Rates of individual components of PoCE	1 and 12 months
Any revascularization	Rates of individual components of PoCE	1 and 12 months
Target vessel failure (TVF)	Target vessel failure is defined as cardiovascular death, target vessel myocardial infraction (TV-MI), and clinically-indicated target vessel revascularization	1 and 12 months
Clinically-indicated target vessel revascularization	Rates of individual components of TVF	1 and 12 months
Definite/Probable stent thrombosis rates		1 and 12 months

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Study Chair: Ling Tao, MD,PHD, Xijing Hospital; Study Chair: Patrick Serruys, MD,PHD, National University of Ireland, Galway; Study Chair: Yoshinobu Onuma, MD,PHD, National University of Ireland, Galway; Study Chair: Chao Gao, MD,PHD, Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 12, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Acute coronary syndrome; Drug-coated balloons; Ticagrelor Monotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor
• Other Study ID Numbers: CAGE-FREE II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No