Antegrade Dissection and Re-entry Versus Retrograde Strategy in CTO PCI (ADRENALINE)

Antegrade Dissection and Re-entry Versus Retrograde Strategy in Chronic Total Occlusion Percutaneous Coronary Intervention

The ADRENALINE trial has been designed as a multi-center, prospective randomized study to compare the procedural and periprocedural outcomes of coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using antegrade dissection and re-entry (ADR) versus retrograde strategy. Beyond the patient-oriented outcomes, the influence of the studied CTO PCI strategies on the stress levels among interventional cardiologists will be explored.

The main questions it aims to answer are as follows:

• What is the difference between ADR versus retrograde strategy with regard to total procedure time, the rates of successful guidewire crossing and periprocedural complications as well as stress levels experienced by interventional cardiologists?
• Is retrograde approach associated with higher rates of myocardial injury/infarction based on cardiac troponin/cardiac magnetic resonance (CMR) as compared with ADR?

Participants will undergo pre- and postprocedural laboratory testing (cardiac troponin, CK-MB), CMR for late gadolinium enhancement and health status assessment. Subjects undergoing successful CTO PCI using antegrade wiring strategy will be included in the observational arm.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Percutaneous Coronary Intervention; Coronary Occlusion
• Intervention / Treatment: Procedure: CTO PCI using ADR strategy; Procedure: CTO PCI using retrograde strategy

Detailed Description

The ADRENALINE trial is planned as a multicenter, prospective randomized research experiment in patients with clinical indication for PCI of CTO. The target population will comprise patients with at least difficult CTO (J-CTO score ≥2) and angiographic equipoise for either ADR or the retrograde CTO recanalization strategy as evaluated by 2 independent CTO PCI operators. The pre-procedural assessment will comprise cardiac magnetic resonance (CMR) for late gadolinium enhancement, laboratory testing (cardiac troponin, creatine kinase-MB) and health status assessed by the Seattle angina questionnaire (SAQ) and the Rose Dyspnea Scale. Subsequently patients with either failed or unattempted primary antegrade wiring strategy will be evenly randomized (1:1 fashion) to either ADR or the retrograde CTO crossing strategy (n=74), while subjects undergoing successful antegrade wiring will be included in the observational arm (n=47). After CTO PCI, the cardiac troponin and creatine kinase-MB will be measured at 12 hours intervals (at least up to 24 hours), while CMR with late gadolinium enhancement will be repeated within 5 days post-procedure (including the observational arm). The health status of the study participants (SAQ and the Rose Dyspnea Scale) will be re-assessed at 3-months post-CTO PCI. In addition, to investigate the effect of the studied CTO PCI strategies on the occupational hazard of interventional cardiologists, the physical and mental stress levels experienced by CTO operators will be continuously monitored during the procedure. The co-primary endpoint is defined as: 1) total procedure time and 2) successful guidewire crossing through CTO. The secondary endpoints include: time of successful guidewire crossing through CTO, final technical success of CTO PCI, radiation dose, contrast volume, equipment cost, procedural complications, rate of periprocedural myocardial injury, rate of new myocardial infarction on CMR, quality of life, target lesion failure (cardiac death, target vessel-related myocardial infarction, and clinically-driven target lesion revascularization) at 3 months follow-up, and stress indices experienced by physicians during the procedure.

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katarzyna Istynowicz; Phone Number: 0048223434268; Email: kistynowicz@ikard.pl
• Study Contact Backup: Name: Wioletta Antos; Phone Number: 0048223434268; Email: wantos@ikard.pl

Study Locations

• Poland
  • Lublin, Poland
    • Recruiting
    • Hospital of the Ministry of the Interior and Administration
    • Contact: Jakub Drozd; Phone Number: 0048817284626; Email: sekretariat@szpitalmsw.pl
  • Lublin, Poland
    • Recruiting
    • 1st Military Clinical Hospital
    • Contact: Grzegorz Sobieszek; Phone Number: 004881261183666
  • Warsaw
    • Warsaw, Warsaw, Poland
      • Recruiting
      • National Institute of Cardiology
      • Contact: Maksymilian Opolski

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• clinical indication for CTO PCI as determined by the local heart team (presence of angina or equivalent symptoms and/or documented ischemia or viability)
• at least difficult native CTO lesion with J-CTO difficulty score ≥2 points on invasive angiography
• angiographic suitability for both ADR and the retrograde strategy as assessed by 2 independent hybrid CTO PCI operators
• informed consent for participation in the study

Exclusion Criteria:

• <18 years of age
• acute myocardial infarction
• cardiogenic shock
• severe valvular disease
• estimated life expectancy <1 year
• contraindication to PCI
• contrast allergy
• positive pregnancy test or breast-feeding
• native CTO lesion with easy or intermediate difficulty score on invasive angiography (J-CTO score <2 points)
• lack of angiographic equipoise between the ADR and the retrograde strategy as assessed by 2 independent hybrid CTO PCI operators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ADR strategy; Patients with either failed or unattempted primary antegrade wiring strategy will be evenly randomized (1:1 fashion) to either ADR or retrograde CTO crossing strategy. The ADR, as part of the antegrade approach, involves extraplaque crossing of the occluded coronary artery with subsequent reentry into the distal true lumen using dedicated reentry systems or knuckle wire techniques.	Procedure: CTO PCI using ADR strategy; CTO recanalization using ADR performed as primary or secondary CTO PCI strategy (i.e. in case of unattempted or failed antegrade wiring, respectively).
Other: Retrograde strategy; Patients with either failed or unattempted primary antegrade wiring strategy will be evenly randomized (1:1 fashion) to either ADR or retrograde CTO crossing strategy. The retrograde technique, planned as the comparator to the ADR strategy, relies on crossing the occluded coronary artery from the distal vessel (i.e. against the original direction of blood flow). Retrograde CTO crossing is attempted either with retrograde intraplaque wiring or more frequently using the retrograde dissection and reentry techniques.	Procedure: CTO PCI using retrograde strategy; CTO recanalization using retrograde approach performed as primary or secondary CTO PCI strategy (i.e. in case of unattempted or failed antegrade wiring, respectively).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total procedure time	Total procedure time in minutes.	procedural (1 day)
Successful guidewire crossing through CTO	Rate of successful guidewire crossing through CTO.	procedural (1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success	Achievement of Thrombolysis In Myocardial Infarction grade 3 flow in all ≥2.5-mm distal branches with <30% residual stenosis.	procedural (1 day)
Time of successful guidewire crossing	Time of successful guidewire crossing through CTO in minutes defined as the time from starting ADR or the retrograde approach to the time of successful CTO recanalization using any technique.	procedural (1 day)
Fluoroscopy time	Fluoroscopy time in minutes.	procedural (1 day)
Radiation dose	Total radiation dose in Gy and mGycm2.	procedural (1 day)
Contrast volume	Total contrast volume in mL.	procedural (1 day)
Cost of CTO PCI	Total cost of CTO PCI procedure in PLN.	procedural (1 day)
Number and type of procedural complications	Total number and specification of procedural complications (death, non-fatal myocardial infarction, cardiac tamponade requiring pericardiocentesis, coronary perforation, stroke, major bleeding according to Bleeding Academic Research Consortium).	procedural (1 day)
Periprocedural myocardial injury	Any periprocedural myocardial injury based on the dynamics of cardiac troponin.	in-hospital (2-5 days)
Periprocedural myocardial infarction	Any periprocedural myocardial infarction based on the dynamics of creatine kinase-MB/cardiac troponin and according to Fourth universal definition of myocardial infarction.	in-hospital (2-5 days)
Myocardial infarction on CMR	Any new myocardial infarction as assessed on serial CMR with late gadolinium enhancement.	in-hospital (2-5 days)
Target lesion failure	Total number of cardiac death, target vessel-related myocardial infarction or clinically-driven target lesion revascularization.	3-months
All-cause death	Any death observed.	3-months
Cardiac death	Any cardiac death observed.	3-months
Target vessel-related myocardial infarction	Any target vessel-related myocardial infarction observed.	3-months
Clinically-driven target lesion revascularization	Any clinically-driven target lesion revascularization observed.	3-months
CCS class	Quality of life assessed by the Canadian Cardiovascular Society (CCS) grading scale measuring the severity of exertional angina (it uses a scale from 1 to 4 where 1 means angina only occurs with strenuous, rapid or prolonged exertion, and 4 means angina is present at rest).	3-months
SAQ score	Quality of life assessed by the Seattle Angina Questionnaire comprising a 19-item questionnaire categorized into five scales (angina frequency, angina stability, physical limitations, treatment satisfaction, and disease-specific quality of life) with each scale transformed to a 0-100 score (the higher the score, the better the quality of life).	3-months
Dyspnea severity on the Rose Dyspnea Scale	Quality of life assessed by the Rose dyspnea scale questionnaire measuring dyspnea complaints or shortness of breath (it consists of a score from 0 to 4, where 0 means no dyspnea complaints and 4 means the patient has complaints during no or minimal physical effort).	3-months
Heart rate	Mean heart rate of the first CTO operator throughout CTO PCI.	operator-related (1 day)
Mean arterial pressure	Mean arterial pressure in mmHg of the first CTO operator throughout CTO PCI.	operator-related (1 day)
Systolic blood pressure	Mean systolic blood pressure in mmHg of the first CTO operator throughout CTO PCI.	operator-related (1 day)
Diastolic blood pressure	Mean diastolic blood pressure in mmHg of the first CTO operator throughout CTO PCI.	operator-related (1 day)
Blood glucose concentration	Continuous blood glucose concentration monitoring in mmol/l of the first CTO operator throughout CTO PCI.	operator-related (1 day)
Brain activity monitoring	Continuous brain activity monitoring via quantitative near infrared spectroscopy system assessing changes in relative concentrations of oxygenated and deoxygenated hemoglobin of the frontal cortex of the first CTO operator throughout CTO PCI.	operator-related (1 day)
Salivary cortisol concentration	Salivary cortisol concentration in ng/mL of the first CTO operator measured at 30-min intervals throughout CTO PCI.	operator-related (1 day)
High-sensitivity cardiac troponin concentration	Changes in the blood concentration of the high-sensitivity cardiac troponin (ng/L) pre- and post-CTO PCI in the first CTO operator.	operator-related (1 day)
Perceived Stress Scale score	Stress level assessment in the first CTO operator adapted to CTO procedure and based on the Perceived Stress Scale score containing 10 questions with a 5-point answer scale ranging from 0 ('never') to 4 ('very often') - the minimum score is 0 (indicating no stress) and the maximum score is 40 (indicating the highest level of stress).	operator-related (1 day)

Collaborators and Investigators

• Sponsor: National Institute of Cardiology, Warsaw, Poland
• Collaborators: Medical Research Agency, Poland
• Investigators: Principal Investigator: Maksymilian Opolski, National Institute of Cardiology

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: March 4, 2025
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 17, 2025

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; coronary artery disease; coronary chronic total occlusion; antegrade dissection and re-entry; retrograde strategy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease; Coronary Occlusion
• Other Study ID Numbers: 2024/ABM/01/00006 (Other Identifier: National Institute of Cardiology, Warsaw, Poland)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No