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CARHEXA: Coronary Arteriogenetic Heparinized Exercise

Sponsor
Clinical Centre of Serbia (Other)
Overall Status
Completed
CT.gov ID
NCT03350737
Collaborator
Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy (Other)
32
Enrollment
1
Location
2
Arms
82.9
Actual Duration (Months)
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Prospective, randomized, open-label study design. These "no-option" patients will be allocated (16 for each group) to 2 treatmentsProspective, randomized, open-label study design. These "no-option" patients will be allocated (16 for each group) to 2 treatments
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Coronary ARteriogenesis With Combined Heparin and EXercise Therapy in Chronic Refractory Angina
Actual Study Start Date :
Feb 1, 2013
Actual Primary Completion Date :
Dec 31, 2019
Actual Study Completion Date :
Dec 31, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Heparin-primed physical rehabilitation

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
Standard treadmill exercise session
Other Names:
  • E

    • Drug: Heparin
    Heparin i.v.
    Other Names:
  • H

    		•
    Placebo Comparator: Placebo-primed physical rehabilitation

    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
    Standard treadmill exercise session
    Other Names:
  • E

    • Other: Placebo
    Sodium Chloride 0.9% i.v.
    Other Names:
  • P

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change from Baseline Canadian Cardiovascular Society (CCS) angina severity class at 2 weeks [2 weeks]

      CCS class ranging from 1 (mild) to 4 (severe) before and after the 2-week physical rehabilitation.

    Secondary Outcome Measures

    1. Change from Baseline peak stress wall motion score index (WMSI) at 2 weeks [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. Change from baseline peak stress global longitudinal strain (GLS) at 2 weeks [2 weeks]

      Peak stress GLS assessed by echocardiography before and after the 2-week physical rehabilitation.

    Other Outcome Measures

    1. Change from Baseline Coronary Collateral Circulation (CCC) at 2 weeks [2 weeks]

      CCC score assessed by multi dimensional computed tomography (CT) before and after 2-week physical rehabilitation. Distal filling of the epicardial segment is semiquantitatively classified by using a four-point scale according to patterns at coronary CT angiography (CTA) (0 = absence of distal filling; 1 = partial distal filling, with a length less than one-third of the segment; 2 = partial distal filling, with a length between one-third and two-thirds of the segment; 3 = complete or partial distal filling, with a length longer than two-thirds of the segment). A coronary CTA scores correspond fully to Rentrop classification (coronary CTA score of 0 or 1 to Rentrop 0 or 1, coronary CTA score of 2 or 3 to Rentrop 2 or 3). Coronary CTA score of 3 is indicative of well-developed collaterals, contrary to scores of 0-2 (poorly developed). Also we look for change in growth of baseline bridging antegrade collaterals at 2 weeks (0= not present, 1= present)

    2. Change from Baseline Stable Angina questionnaire (SAQ) at 4 weeks [2 weeks to one month]

      19-item Seattle SAQ that assesses angina frequency, angina stability, physical limitations, treatment satisfaction, and disease perception/QoL

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Centre of Serbia Belgrade Serbia 11000

    Sponsors and Collaborators

    • Clinical Centre of Serbia
    • Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy

    Investigators

    • Principal Investigator: Branko Beleslin, MD, PhD, Clinical Centre of Serbia
    • Study Director: Ana Djordjevic-Dikic, MD, PhD, Clinical Centre of Serbia
    • Study Chair: Eugenio Picano, MD, PhD, Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Branko Beleslin, Clinical research, Clinical Centre of Serbia
    ClinicalTrials.gov Identifier:
    NCT03350737
    Other Study ID Numbers:
    • 128/8
    First Posted:
    Nov 22, 2017
    Last Update Posted:
    May 13, 2020
    Last Verified:
    May 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Branko Beleslin, Clinical research, Clinical Centre of Serbia
    No-option patients
    Additional relevant MeSH terms:
    Angina Pectoris
    Angina, Stable
    Heparin

    Study Results

    No Results Posted as of May 13, 2020