Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy | OTHER_GOV |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Physical rehabilitation | Other | Standard treadmill exercise session |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline Coronary Collateral Circulation (CCC) at 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) |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Centre of Serbia | Belgrade | 11000 | Serbia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11078227 | Background | 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. | |
| 14967718 | 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. |
Not provided
Not provided
De-identified individual participant data for all primary and secondary outcome measures will be made available.
After the study completion.
For collaborators, data analyses upon request.
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 25, 2012 | Nov 13, 2017 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000787 | Angina Pectoris |
| D060050 | Angina, Stable |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D006493 | Heparin |
| D011522 | Protons |
| ID | Term |
|---|---|
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D002414 | Cations, Monovalent |
Not provided
Not provided
Prospective, randomized, open-label study design. These "no-option" patients will be allocated (16 for each group) to 2 treatments
Not provided
Not provided
Not provided
Not provided
| Heparin | Drug | Heparin i.v. |
|
|
| Placebo | Other | Sodium Chloride 0.9% i.v. |
|
|
Peak stress GLS assessed by echocardiography before and after the 2-week physical rehabilitation. |
| 2 weeks |
| 2 weeks |
| Change from Baseline Stable Angina questionnaire (SAQ) at 4 weeks | 19-item Seattle SAQ that assesses angina frequency, angina stability, physical limitations, treatment satisfaction, and disease perception/QoL | 2 weeks to one month |
| 9373049 | 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. |
| 11390835 | 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. |
| 2834115 | 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. |
| 12515758 | 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. |
| 11846493 | 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. |
| 19770393 | 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. |
| 12383579 | 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. |
| 9093537 | 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. |
| 11549300 | 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. |
| 3156171 | 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. |
| 19144878 | 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. |
| 19001473 | 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. |
| 11382729 | 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. |
| 20855668 | 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. |
| 20432394 | 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. |
| 19736553 | 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. |
| D002637 |
| Chest Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002412 |
| Cations |
| D007477 | Ions |
| D004573 | Electrolytes |
| D007287 | Inorganic Chemicals |
| D006859 | Hydrogen |
| D004602 | Elements |
| D005740 | Gases |
| D000071940 | Nucleons |
| D004601 | Elementary Particles |
| D055585 | Physical Phenomena |