Randomized Comparison of Optimal Medical Therapy and Percutaneous Recanalization for Chronic Total Occlusion (COMET-CTO)
Condition: Chronic Total Occlusions of Coronary Arteries
Study type: Interventional
Phase: Phase 4

Summary: 
      Several meta analysis comparing successful Percutaneous Coronary Intervention of Chronic
      Total Occlusion (PCI-CTO) with unsuccessful PCI-CTO showed that there is significant
      reduction in short-term and long-term mortality. To our knowledge till today no prospective
      randomized trial compared percutaneous revascularization of CTO with optimal medical therapy.
      For this reason quality of live improvement is one of the most important indications for
      revascularization in elective patients with CTO. In contemporary literature Seattle Angina
      Questionnaire (SAQ) is a psychometrically solid disease-specific instrument designed to
      assess the functional status of patients with angina. It comprises 19 questions that quantify
      five clinically relevant domains: physical limitation, angina stability, angina frequency,
      treatment satisfaction and disease perception/quality of life.

      In this open prospective study patients with CTO of coronary artery will be randomized in two
      groups: first - patients with percutaneous coronary intervention of chronic total occlusion
      with optimal medical therapy and second group - patients with only optimal medical therapy
      (control group). Primary endpoint will be quality of life and secondary endpoints will be
      mayor adverse cardiovascular events (MACE). All patients will complete Seattle Angina
      Questionnaire before randomization and after 6 months of follow-up.
    

Detailed description: 
      Coronary artery chronic total occlusion (CTO) is defined as complete occlusion of coronary
      arteries that lasts for more than three months (TIMI 0 coronary flow in occluded segment). In
      absence of serial angiograms , occlusion duration can be assumed based on clinical data
      regarding event that caused occlusion. Consensus document from the Euro CTO club suggests 3
      levels of certainty:

      a) Certain (angiographically confirmed): the minority of cases where a previous angiogram
      (for instance before a previous CABG operation, or after an acute myocardial infarction) has
      confirmed the presence of TIMI 0 flow for > 3 months prior to the planned procedure; b)
      Likely (clinically confirmed): objective evidence of an acute myocardial infarction in the
      territory of the occluded artery without other possible culprit arteries >3 months before the
      current angiogram; c) Possible (undetermined): a CTO with TIMI 0 flow and angiographic
      anatomy suggestive of long-standing occlusion (collateral development, no contrast staining)
      with stable angina symptoms unchanged in the last 3 months or evidence of silent ischemia; in
      case of recent acute ischemic episodes (acute myocardial infarction or unstable angina or
      worsening effort angina), a culprit artery other than the occluded vessel should be present.

      CTO is an often finding. In spite of that, there is uncertainty should this lesions be
      revascularized and in what way. If there are symptoms or objective proof of ischemia and
      viability in the area of occluded artery distribution, recanalization of CTO should be
      considered. Several studies showed that in the presence of chronic total occlusion collateral
      circulation may produce supply of oxygen and preserve viability. However assessment of
      collateral circulation with adenosine stress test showed abnormal coronary reserve in over
      than 90% was reduced which means that collaterals are not enough Therapeutically
      uncertainties lead partially from technical complex procedures of revascularization CTO with
      PCI, with success rate of 60-70% which is importantly lower than revascularization rate of
      non-CTO lesions (98%). During last decade there has been significant improvement in
      technology, equipment and techniques of percutaneous revascularization procedures for CTO
      that increased procedural success rate (around 90%). On the other hand there are separate
      views regarding possibility of treating this patients with coronary artery bypass graft
      (CABG), and specially patients with single coronary disease Metaanalysis performed by
      O'Connor SA et al. showed that presence of chronic total occlusion on non infarct artery in
      patients with acute myocardial infarction significantly increases mortality. Furthermore
      several mataanalyses that analyzed the effect of PCI CTO on survival, showed significant
      reduction of mortality rate in short term and also long term follow up. Studies enrolled in
      this metaanalyses were retrospective or prospective registries which compared successful PCI
      CTO with PCI CTO failure.

      There are different explanations for this clinical result (mortality reduction):

        1. direct benefit of achieving coronary flow and myocardial perfusion improves ventricular
           function and reduces risk of malignant arrhythmias

        2. patients in which PCI was unsuccessful probably have more serious coronary
           atherosclerosis and fibrosis that contribute to procedural failure and greater mortality
           (3).

      Similar to previous metaanalyses study conducted by Prasada et al. showed significantly
      greater mortality in the group with procedural failure .

      Study conducted by Hoye et al. showed significant increase of 5-year mortality rate, CABG and
      MACE in the group with procedural failure. Authors explained the difference in survival by
      pharmacological management that can be confounding factor. Also authors stated that better
      prognosis after successful procedure is probably related to improved left ventricular
      function and reduced risk of malignant arrhythmias. To our knowledge, there is no prospective
      randomized study which compared PCI CTO with optimal medical therapy. For this reason quality
      of life improvement is one of the most important indication for revascularization CTO in
      elected patients. However, in contemporary literature there is little data regarding quality
      of life assessment in patients with CTO.

      Quality of life assessment is important indicator of successful revascularization in patients
      with coronary artery disease. "Seattle Angina Questionnaire" (SAQ) is validated for quality
      of life assessment in patients with coronary artery disease. This questionnaire is based on
      five different domains : physical limitation, angina stability, angina frequency, treatment
      satisfaction, and disease perception. So far quality of life assessment with SAQ was used in
      four studies. Two of them compared results of SAQ in patients with successful recanalization
      of CTO and patients with procedural failure. They proved significant improvement in SAQ score
      in patients with recanalized CTO. Third study compared revascularization strategies (PCI vs.
      CABG) with optimal medical therapy in patients with diagnosed CTO. In the group treated with
      medical therapy there were no changes in scores of SAQ domains after one year follow-up,
      while in patients that were revascularized in CTO territory improvement in SAQ scores were
      documented in three domains (Physical restraint, angina frequency and disease perception).
      Fourth study compared quality of life after CTO PCI vs.PCI in on non CTO lesion. In both
      groups similar improvement was documented in all domains during 6 months follow-up.

      So far no prospective randomized study was conducted that examined quality of life in
      patients with CTO.
    

Intervention name(s): Percutaneous coronary intervention; Optimal medical therapy
Intervention type(s): Procedure; Drug
Intervention description(s): Recanalisation of chronic total occlusion of coronary artery; Medical threatment according to guidelines
Other intervention name(s): PCI; Angina pectoris opetimal medical therapy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment