Coronary Arteriogenetic Heparinized Exercise

NCT03350737 | Completed

• 1 other identifier: 128/8
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory Angina; Chronic Stable Angina

Keywords

No-option patients

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Change from Baseline peak stress wall motion score index (WMSI) at 2 weeks

  2 weeks

• Change from baseline peak stress global longitudinal strain (GLS) at 2 weeks

  2 weeks

Other Outcomes (2)

• Change from Baseline Coronary Collateral Circulation (CCC) at 2 weeks

  2 weeks

• Change from Baseline Stable Angina questionnaire (SAQ) at 4 weeks

  2 weeks to one month

Study Arms (2)

Heparin-primed physical rehabilitation

EXPERIMENTAL

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; Drug: Heparin

Placebo-primed physical rehabilitation

PLACEBO COMPARATOR

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; Other: Placebo

Interventions

Physical rehabilitation OTHER

Standard treadmill exercise session

Also known as: E

Heparin-primed physical rehabilitation; Placebo-primed physical rehabilitation

Heparin DRUG

Heparin i.v.

Also known as: H

Heparin-primed physical rehabilitation

Placebo OTHER

Sodium Chloride 0.9% i.v.

Also known as: P

Placebo-primed physical rehabilitation

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with documented coronary artery disease not amenable of future treatment and belonging to "no-option" category with symptoms consistent with angina pectoris

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Clinical Centre of Serbia

Belgrade, 11000, Serbia

Location

Related Publications (18)

• Barron HV, Sciammarella MG, Lenihan K, Michaels AD, Botvinick EH. Effects of the repeated administration of adenosine and heparin on myocardial perfusion in patients with chronic stable angina pectoris. Am J Cardiol. 2000 Jan 1;85(1):1-7. doi: 10.1016/s0002-9149(99)00596-2.

  PMID: 11078227 BACKGROUND

• Bolognese L, Carrabba N, Parodi G, Santoro GM, Buonamici P, Cerisano G, Antoniucci D. Impact of microvascular dysfunction on left ventricular remodeling and long-term clinical outcome after primary coronary angioplasty for acute myocardial infarction. Circulation. 2004 Mar 9;109(9):1121-6. doi: 10.1161/01.CIR.0000118496.44135.A7. Epub 2004 Feb 16.

  PMID: 14967718 BACKGROUND

• Bombardini T, Picano E. The coronary angiogenetic effect of heparin: experimental basis and clinical evidence. Angiology. 1997 Nov;48(11):969-76. doi: 10.1177/000331979704801106.

  PMID: 9373049 BACKGROUND

• Buschmann I, Schaper W. Arteriogenesis Versus Angiogenesis: Two Mechanisms of Vessel Growth. News Physiol Sci. 1999 Jun;14:121-125. doi: 10.1152/physiologyonline.1999.14.3.121.

  PMID: 11390835 BACKGROUND

• 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.

  PMID: 2834115 BACKGROUND

• Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, Ferguson TB Jr, Fihn SD, Fraker TD Jr, Gardin JM, O'Rourke RA, Pasternak RC, Williams SV, Gibbons RJ, Alpert JS, Antman EM, Hiratzka LF, Fuster V, Faxon DP, Gregoratos G, Jacobs AK, Smith SC Jr; American College of Cardiology; American Heart Association Task Force on Practice Guidelines. Committee on the Management of Patients With Chronic Stable Angina. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). Circulation. 2003 Jan 7;107(1):149-58. doi: 10.1161/01.cir.0000047041.66447.29. No abstract available.

  PMID: 12515758 BACKGROUND

• Mannheimer C, Camici P, Chester MR, Collins A, DeJongste M, Eliasson T, Follath F, Hellemans I, Herlitz J, Luscher T, Pasic M, Thelle D. The problem of chronic refractory angina; report from the ESC Joint Study Group on the Treatment of Refractory Angina. Eur Heart J. 2002 Mar;23(5):355-70. doi: 10.1053/euhj.2001.2706. No abstract available.

  PMID: 11846493 BACKGROUND

• Meier P, Gloekler S, de Marchi SF, Indermuehle A, Rutz T, Traupe T, Steck H, Vogel R, Seiler C. Myocardial salvage through coronary collateral growth by granulocyte colony-stimulating factor in chronic coronary artery disease: a controlled randomized trial. Circulation. 2009 Oct 6;120(14):1355-63. doi: 10.1161/CIRCULATIONAHA.109.866269. Epub 2009 Sep 21.

  PMID: 19770393 BACKGROUND

• Picano E, Alaimo A, Chubuchny V, Plonska E, Baldo V, Baldini U, Pauletti M, Perticucci R, Fonseca L, Villarraga HR, Emanuelli C, Miracapillo G, Hoffmann E, De Nes M. Noninvasive pacemaker stress echocardiography for diagnosis of coronary artery disease: a multicenter study. J Am Coll Cardiol. 2002 Oct 2;40(7):1305-10. doi: 10.1016/s0735-1097(02)02157-5.

  PMID: 12383579 BACKGROUND

• Picano E, Michelassi C. Chronic oral dipyridamole as a 'novel' antianginal drug: the collateral hypothesis. Cardiovasc Res. 1997 Mar;33(3):666-70. doi: 10.1016/s0008-6363(96)00262-3.

  PMID: 9093537 BACKGROUND

• 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.

  PMID: 11549300 BACKGROUND

• 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.

  PMID: 3156171 BACKGROUND

• Schirmer SH, van Nooijen FC, Piek JJ, van Royen N. Stimulation of collateral artery growth: travelling further down the road to clinical application. Heart. 2009 Mar;95(3):191-7. doi: 10.1136/hrt.2007.136119.

  PMID: 19144878 BACKGROUND

• Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, Voigt JU, Zamorano JL; European Association of Echocardiography. Stress Echocardiography Expert Consensus Statement--Executive Summary: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur Heart J. 2009 Feb;30(3):278-89. doi: 10.1093/eurheartj/ehn492. Epub 2008 Nov 11. No abstract available.

  PMID: 19001473 BACKGROUND

• 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.

  PMID: 11382729 BACKGROUND

• Traupe T, Gloekler S, de Marchi SF, Werner GS, Seiler C. Assessment of the human coronary collateral circulation. Circulation. 2010 Sep 21;122(12):1210-20. doi: 10.1161/CIRCULATIONAHA.109.930651. No abstract available.

  PMID: 20855668 BACKGROUND

• 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.

  PMID: 20432394 BACKGROUND

• 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.

  PMID: 19736553 BACKGROUND

MeSH Terms

Conditions

Angina Pectoris; Angina, Stable

Interventions

Heparin; Protons

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena

Study Officials

• Branko Beleslin, MD, PhD

  Clinical Centre of Serbia

  PRINCIPAL INVESTIGATOR

• Ana Djordjevic-Dikic, MD, PhD

  Clinical Centre of Serbia

  STUDY DIRECTOR

• Eugenio Picano, MD, PhD

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical research

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

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: November 22, 2017
• Study Start: February 1, 2013
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: May 13, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After the study completion.
• Access Criteria: For collaborators, data analyses upon request.

Locations

SE (1)