Coronary Arteriogenetic Heparinized Exercise (CARHEXA)

May 12, 2020 updated by: Branko Beleslin, Clinical Centre of Serbia

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

32

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Serbia
      • Belgrade, Serbia, 11000
        • Clinical Centre of Serbia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline Coronary Collateral Circulation (CCC) at 2 weeks
Time Frame: 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 weeks
Change from Baseline Stable Angina questionnaire (SAQ) at 4 weeks
Time Frame: 2 weeks to one month
19-item Seattle SAQ that assesses angina frequency, angina stability, physical limitations, treatment satisfaction, and disease perception/QoL
2 weeks to one month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinical Centre of Serbia

Collaborators

Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2013

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

December 31, 2019

Study Registration Dates

First Submitted

November 8, 2017

First Submitted That Met QC Criteria

November 17, 2017

First Posted (Actual)

November 22, 2017

Study Record Updates

Last Update Posted (Actual)

May 13, 2020

Last Update Submitted That Met QC Criteria

May 12, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 128/8

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data for all primary and secondary outcome measures will be made available.

IPD Sharing Time Frame

After the study completion.

IPD Sharing Access Criteria

For collaborators, data analyses upon request.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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