A Randomized Multicentre Trial to Evaluate the Utilization of Revascularization or Optimal Medical Therapy for the Treatment of Chronic Total Coronary Occlusions

Study Overview
=================
Brief Summary
-----------------
CTOs are common among patients with angina, and are detected in around 20% of patients undergoing coronary angiography. Treatment of CTO has been found to constitute only 7% of PCI practice on average. One of the reasons for the under-presentation of CTOs in PCI target lesions is the lack of evidence-based medical data on treatment indications, and the continued low level of accepted evidence for the treatment of CTOs by PCI in PCI guidelines. Patients with a CTO represent patients with stable coronary artery disease. The COURAGE trial comparing PCI with optimal medical therapy in stable coronary disease did not show a difference in mortality or myocardial infarction between the two treatment options. However, CTOs were not included in the COURAGE trial. But that trial did confirm the superiority of PCI over OMT in controlling symptoms of angina, with a high cross-over rate to PCI. Whether PCI for CTO is superior to OMT in reducing MACE in those patients with a large ischaemic burden has never been tested in a randomized controlled trial. While there is compelling evidence from registry studies of a clinical and prognostic benefit following successful PCI of CTO compared with PCI failure, there has been no randomized controlled trial of contemporary PCI using drug-eluting stents versus optimal medical therapy. The COURAGE trial nuclear sub-study confirms both that prognosis is closely related to the extent of residual ischaemia and that PCI is more effective in reducing residual ischaemia than optimal medical therapy alone. This confirms earlier retrospective data suggesting that the benefit of PCI is greatest in patients with moderate (10-20%) or severe (>20%) ischaemia. Study hypothesis: PCI with Biolimus eluting stent implantation plus OMT will be superior to OMT alone in improving health status at 12-month follow-up, and will be noninferior with respect to the composite of all cause death/ non fatal MI at 36-month follow up, in patients with a CTO in an epicardial coronary artery >2.5 mm diameter and chronic stable angina with evidence of ischemia and viability in the territory subtended by the CTO

Official Title
-----------------
A Randomized Multicentre Trial to Evaluate the Utilization of Revascularization or Optimal Medical Therapy for the Treatment of Chronic Total Coronary Occlusions

Conditions
-----------------
Chronic Stable Angina, Dyspnea, Coronary Occlusion

Intervention / Treatment
-----------------
* Device: Biolimus-eluting stent implantation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years of age with written informed consent CTO in native coronary artery a) Stable angina, or b) myocardial ischaemia in a territory supplied by CTO, and c) viability in akinetic myocardium (<50% transmural late enhancement on MRI or normal resting perfusion scan) CTO located in segments 1-3 (RCA), 6-7 (LAD), 11-12 (LCx) target artery ≥2.5mm Exclusion Criteria: AMI or NSTE-ACS within 1 month Significant untreated coronary stenosis in a territory other than CTO Patients with MVD and significant non-CTO stenoses where it is deemed unsafe to treat the non-CTO lesion first (e.g. Significant proximal LAD lesion with chronically occluded RCA) Patient unsuitable for 12 month dual anti-platelet therapy Any exclusion criteria for PCI or DES Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following index procedure

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Biolimus-eluting stent implantation<br>PCI of CTO using a Biomatrix drug-eluting stent system + optimal medical therapy. | Device: Biolimus-eluting stent implantation<br>* Recanalization of chronic coronary artery occlusion and subsequent implantation of one or ore Biosensor stents<br>* Other names: Biosensors Biolimus-eluting stents of all sizes and lengths;|
| No Intervention: Medical therapy<br>Optimal medical therapy. Subsequent PCI only if symptoms of angina persist despite optimal medical therapy. At least 2 anti-anginal agents or the maximum tolerated anti-anginal therapy should be used before crossover. Medical therapy should include adequate ventricular rate-limiting medication (i.e. Beta-blocker or rate-limiting calcium antagonist) where appropriate. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Seattle Angina Questionnaire (SAQ) | Seattle Angina Questionnaire and EQ-5D for health outcomes measurement | Baseline and 12 months | 
| Major cardiovascular events | Cumulative composite endpoint of cardiovascular death, non-fatal MI at 3 years | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and efficacy endpoints | All cause mortality Cardiac mortality Myocardial Infarction Any hospitalization due to cardiovascular events (angina, congestive heart failure, arrythmias) Repeat revascularization | 12 and 36 months | 
| Procedural complications | Incl. periprocedural enzyme leak (defined by CK increase >3 times ULN); pericprocedural MI (new Q-wave or STEMI); pericardial tamponade, need for urgent CABG, CIN, death within 30 days, proven periprocedural cerebrovascular events | baseline upto 36 months | 
| Protocol adherence | Need to cross from OMT to PCI in Group 2 (after escalation up to maximum tolerated anti-anginal therapy and persistent unequivocal symptoms) | 36 months | 
| Per protocol analysis | primary endpoint comparison in patients who did have a successful revascularization compared to those patients treated medically who had no subsequent PCI | 36 months |