Coronary Arteriogenetic Heparinized Exercise

NCT ID: NCT03350737

Last Updated: 2020-05-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-02-01

Study Completion Date

2019-12-31

Brief Summary

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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

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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.

Conditions

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Refractory Angina Chronic Stable Angina

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, randomized, open-label study design. These "no-option" patients will be allocated (16 for each group) to 2 treatments
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Physical rehabilitation

Intervention Type OTHER

Standard treadmill exercise session

Heparin

Intervention Type DRUG

Heparin i.v.

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

Group Type PLACEBO_COMPARATOR

Physical rehabilitation

Intervention Type OTHER

Standard treadmill exercise session

Placebo

Intervention Type OTHER

Sodium Chloride 0.9% i.v.

Interventions

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Physical rehabilitation

Standard treadmill exercise session

Intervention Type OTHER

Heparin

Heparin i.v.

Intervention Type DRUG

Placebo

Sodium Chloride 0.9% i.v.

Intervention Type OTHER

Other Intervention Names

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E H P

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

OTHER_GOV

Sponsor Role collaborator

Clinical Centre of Serbia

OTHER

Sponsor Role lead

Responsible Party

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Branko Beleslin

Clinical research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Branko Beleslin, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Clinical Centre of Serbia

Ana Djordjevic-Dikic, MD, PhD

Role: STUDY_DIRECTOR

Clinical Centre of Serbia

Eugenio Picano, MD, PhD

Role: STUDY_CHAIR

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

Locations

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Clinical Centre of Serbia

Belgrade, , Serbia

Site Status

Countries

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Serbia

References

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Fujita M, Sasayama S, Asanoi H, Nakajima H, Sakai O, Ohno A. Improvement of treadmill capacity and collateral circulation as a result of exercise with heparin pretreatment in patients with effort angina. Circulation. 1988 May;77(5):1022-9. doi: 10.1161/01.cir.77.5.1022.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Picano E; PISA (Persantin In Stable Angina) study group. Dipyridamole in chronic stable angina pectoris; a randomized, double blind, placebo-controlled, parallel group study. Eur Heart J. 2001 Oct;22(19):1785-93. doi: 10.1053/euhj.2001.2623.

Reference Type BACKGROUND
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Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol. 1985 Mar;5(3):587-92. doi: 10.1016/s0735-1097(85)80380-6.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 19001473 (View on PubMed)

Tateno S, Terai M, Niwa K, Jibiki T, Hamada H, Yasukawa K, Honda T, Oana S, Kohno Y. Alleviation of myocardial ischemia after Kawasaki disease by heparin and exercise therapy. Circulation. 2001 May 29;103(21):2591-7. doi: 10.1161/01.cir.103.21.2591.

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PMID: 20855668 (View on PubMed)

Williams B, Menon M, Satran D, Hayward D, Hodges JS, Burke MN, Johnson RK, Poulose AK, Traverse JH, Henry TD. Patients with coronary artery disease not amenable to traditional revascularization: prevalence and 3-year mortality. Catheter Cardiovasc Interv. 2010 May 1;75(6):886-91. doi: 10.1002/ccd.22431.

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Wykrzykowska JJ, Henry TD, Lesser JR, Schwartz RS. Imaging myocardial angiogenesis. Nat Rev Cardiol. 2009 Oct;6(10):648-58. doi: 10.1038/nrcardio.2009.157. Epub 2009 Sep 8.

Reference Type BACKGROUND
PMID: 19736553 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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128/8

Identifier Type: -

Identifier Source: org_study_id

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