Coronary Arteriogenetic Heparinized Exercise

Study Overview
=================
Brief Summary
-----------------
This study evaluates the addition of heparin to a 2-week cycle of physical rehabilitation in the treatment of refractory angina. Half of the patients will undergo heparin-primed physical rehabilitation, while the other half will undergo only physical rehabilitation.

Detailed Description
-----------------
Our approach is based on the combination of pharmacological stimuli (with heparin) on top of a 2-week cycle of physical rehabilitation. The rationale for this chemical-physical cocktail stems from the fact that increase in shear stress (achieved with exercise), or heparin (when used alone) have no significant effect on coronary arteriogenesis. Nevertheless, when the two stimuli are coupled coronary arteriogenesis is consistently present, and clinically significant. The basic principle of heparin treatment is to potentiates angiogenic growth factors, which are over expressed by increased shear stress at the site of pre-existing collateral vessels as a result of exercise or pacing. Although the precise mechanisms by which heparin potentiates arteriogenesis remain to be completely elucidated, heparin administration combined with exercise has great potential in treating patients with effort angina who are not indicated for conventional revascularization therapy.

Official Title
-----------------
Coronary ARteriogenesis With Combined Heparin and EXercise Therapy in Chronic Refractory Angina

Conditions
-----------------
Chronic Stable Angina, Refractory Angina

Intervention / Treatment
-----------------
* Other: Physical rehabilitation
* Drug: Heparin
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with documented coronary artery disease not amenable of future treatment and belonging to no-option category with symptoms consistent with angina pectoris Exclusion Criteria: Patients with unstable angina, recent myocardial infarction, uncontrolled hypertension, hemodynamically valvular heart disease, bronchial asthma, and neurologic and/or orthopedic illnesses that limit exercise capacity . Patients receiving vitamin K antagonist. Patients actively involved in programmes of cardiac rehabilitation or exercise training.
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
Interventional Model Description: Prospective, randomized, open-label study design. These no-option patients will be allocated (16 for each group) to 2 treatments
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heparin-primed physical rehabilitation<br>2 exercise sessions per day for 5 days a week for 2 weeks with 100 IU/kg of Heparin i.v. (up to a maximum of 5000 IU) 10 minutes prior to exercise | Other: Physical rehabilitation<br>* Standard treadmill exercise session<br>* Other names: E;Drug: Heparin<br>* Heparin i.v.<br>* Other names: H;|
| Placebo Comparator: Placebo-primed physical rehabilitation<br>2 exercise sessions per day for 5 days a week for 2 weeks with placebo (2 ml of Sodium Chloride 0.9% i.v.) 10 minutes prior to exercise | Other: Physical rehabilitation<br>* Standard treadmill exercise session<br>* Other names: E;Other: Placebo<br>* Sodium Chloride 0.9% i.v.<br>* Other names: P;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Canadian Cardiovascular Society (CCS) angina severity class at 2 weeks | CCS class ranging from 1 (mild) to 4 (severe) before and after the 2-week physical rehabilitation. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline peak stress wall motion score index (WMSI) at 2 weeks | Peak WMSI at stress echocardiography before and after 2-week physical rehabilitation at . Wall motion score index is assessed by using 17- segment model of left ventricle (1=normal, 4=dyskinetic). | 2 weeks | 
| Change from baseline peak stress global longitudinal strain (GLS) at 2 weeks | Peak stress GLS assessed by echocardiography before and after the 2-week physical rehabilitation. | 2 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
No-option patients