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Refractory AnginaPhase 2NCT00820586

Intramyocardial Delivery of Autologous Bone Marrow

A Phase 2 study testing Mononuclear bone marrow derived cells in people with Refractory Angina, run by IRCCS San Raffaele at 1 site in Italy.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

A randomized study to assess the safety, feasibility and effectiveness of direct intramyocardial percutaneous delivery of autologous bone marrow-derived total mononuclear cells or selected CD34+ cells in patients with refractory angina pectoris. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Refractory Angina
What is being tested?
Mononuclear bone marrow derived cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteItaly
Study dates
May 2007to Dec 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects >21 years old;
  • Subjects with functional class (CCS) III or IV angina;
  • Subjects with left ventricular (LV) ejection fraction ³ 30%
  • Attempted "best" tolerated medical therapy
  • Clinical signs and symptoms of myocardial ischemia with reversible ischemia on perfusion imaging;
  • Patient deemed to be a poor candidate or at high surgical risk;
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  • Subject must be able to complete a minimum of 2 minutes but no more than 10 minutes exercise test (Bruce Protocol);
  • Subject (or their legal guardian) understands the nature of the procedure and provides written consent prior to the procedure;
  • Subject is willing to comply with specified follow-up evaluations;
  • Patient must develop angina and a horizontal or down-sloping ST-segment depression of ³ 1 mm during exercise, compared to pre-exercise ST segment, 80 ms from the J point or moderate angina with or without the above ST segment changes.
  • Angiographic Inclusion Criteria:
  • Severe obstruction (lumen diameter stenosis > 70%) in a coronary or surgical conduit felt to be solely or partially responsible for angina and myocardial ischemia;
  • There must be at least one coronary or surgical conduit with < 70% diameter stenosis
  • Poor candidate for percutaneous coronary intervention of treatment zone
  • Poor candidates for surgical revascularization procedures, such as inadequate target coronary anatomy or lack of potential surgical conduits.

Who cannot join

  • Pregnant women;
  • Left ventricular ejection fraction <30% as assessed by either echocardiography or left ventriculography;
  • Severe cardiac heart failure with NYHA functional class III-IV symptoms;
  • Chronic atrial fibrillation;
  • Prosthetic aortic valve;
  • Severe (grade III-IV) mitral or aortic insufficiency;
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  • Wall thickness of <8 mm (defined by echocardiography) of the proposed target region of myocardium;
  • Severe co-morbidity associated with a reduction in life expectancy of <1 year, such as chronic medical illnesses
  • Braunwald class II unstable angina
  • Severe peripheral (or aortic) vascular disease which might increase the risk of vascular complications (perforation, dissection or embolization);
  • Significant aortic valve pathologic sclerosis or stenosis
  • LV thrombus (mobile or mural-based) seen on echocardiography;
  • Recent (within 4 weeks) documented myocardial infarction (Q and/or non-Q wave) defined as CK-MB >3times upper normal level;
  • Currently enrolled in another investigational device or drug trial that has not completed the required follow-up period;
  • Thrombocytopenia or history of heparin-induced thrombocytopenia or thrombocytosis
  • Leukopenia
  • Leukocytosis
  • Anemia or erythrocytosis
  • Active peptic ulcer or active gastrointestinal bleeding;
  • Chronic renal failure requiring dialysis;
  • Prior or current malignancy
  • Other conditions that can significantly affect the bone-marrow
  • Evidence of concurrent infection (WBC >12.000 mm3, temperature >38.5° C);
  • Serological of clinical evidence of HIV
  • Immunotherapy
  • Abnormal bone-marrow morphology as evident in bone-marrow smear prior to the intervention
  • Angiographic/Ventriculographic Exclusion Criteria:
  • LV thrombus (mobile or mural-based) seen on left ventriculography;
  • Coronary lesions suitable for percutaneous coronary interventions;
  • Unprotected left main coronary artery disease

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • IRCCS S. Raffaele

    Milan, 20132

Other trials in Italy

About this study

A randomized study to assess the safety, feasibility and effectiveness of direct intramyocardial percutaneous delivery of autologous bone marrow-derived total mononuclear cells or selected CD34+ cells in patients with refractory angina pectoris.

Read the detailed description

Primary Endpoint: Incidence of major adverse cardiac events (MACE) at 30 days. MACE is defined as a combined endpoint of death, acute MI (Q-wave and non-Q wave), revascularization procedures (percutaneous or surgical), and peri-procedural complications (that is, left ventricular perforation with hemodynamic consequences requiring pericardiocentesis, and stroke).

Incidence of MACE at 3, 6 and 12 months

Secondary Endpoints:

  • Change in Canadian Cardiovascular Society (CCS) angina classification score from baseline to 12 months
  • Changes in the quality of life, as assessed according to the Seattle Angina Questionnaire
  • Change in exercise duration and exercise tolerance using standardized treadmill exercise testing from baseline, to 6 months and to 12 months
  • Cumulative number of hospitalizations for coronary ischemia and congestive heart failure at 12 months following treatment.
  • SPECT-chances in global and regional radionuclide perfusion at rest, peak stress, and redistribution for baseline to 1, 6 and 12 months
  • Change in angiographic collateral score at 6 months
  • Change in global and regional myocardial contractility (assessed by echocardiography) at baseline, 6 and 12 months.
Being tested
Mononuclear bone marrow derived cells
Keywords
Intramyocardial, Autologous, Bone, Marrow, Randomized, Percutaneous, CD34+, Refractory, Angina, Pectoris.
Medical subject headings
Angina Pectoris

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mononuclear bone marrow derived cellsProcedure or surgery

    Also called Selected CD34+ bone marrow derived cells

    Direct intramyocardial percutaneous delivery of autologous bone marrow-derived total mononuclear cells or selected CD34+ cells

Study groups in NCT00820586
Study groupRoleWhat they receive
Mononuclear bone marrow derived cellsExperimentalIntramyocardial injection of total mononuclear bone marrow derived cells
Receives: Procedure: Mononuclear bone marrow derived cells
Selected CD34+ bone marrow derived cellsExperimentalIntramyocardial injection of selected CD34+ bone marrow derived cells
Receives: Procedure: Mononuclear bone marrow derived cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of major adverse cardiac events (MACE), defined as a combined endpoint of death, acute MI (Q-wave and non-Q wave), revascularization procedures and peri-procedural complications.

    Measured: 1, 6, 12 months

Secondary outcomes (7)

  1. Change in Canadian Cardiovascular Society (CCS) angina classification score

    Measured: 12 months

  2. Changes in the quality of life, as assessed according to the Seattle Angina Questionnaire

    Measured: 1,3,6,12 months and every year for 8 years

  3. Change in exercise duration and exercise tolerance using standardized treadmill exercise testing

    Measured: 6,12 months

  4. Cumulative number of hospitalizations for coronary ischemia and congestive heart failure

    Measured: 12 months

  5. SPECT-chances in global and regional radionuclide perfusion at rest, peak stress, and redistribution

    Measured: 1, 6, 12 months

  6. Change in angiographic collateral score

    Measured: 6 months

  7. Change in global and regional myocardial contractility (assessed by echocardiography)

    Measured: 6, 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2009 (estimated)
  2. Study startMay 2007
  3. Primary completionJan 2011
  4. Study completionDec 2018 (estimated)

Why it stopped: No more funding support for additional procedures

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00820586
Sponsor's protocol ID
TVICPR-003
Status last verified
Feb 2012
First submitted
8 Jan 2009
Last updated
2 Feb 2012
Results posted
No
Data monitoring committee
No

Publications

  • Losordo DW, Vale PR, Isner JM. Gene therapy for myocardial angiogenesis. Am Heart J. 1999 Aug;138(2 Pt 2):S132-41. doi: 10.1016/s0002-8703(99)70333-9.

    PubMed 10426872

  • Simons M, Bonow RO, Chronos NA, Cohen DJ, Giordano FJ, Hammond HK, Laham RJ, Li W, Pike M, Sellke FW, Stegmann TJ, Udelson JE, Rosengart TK. Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary. Circulation. 2000 Sep 12;102(11):E73-86. doi: 10.1161/01.cir.102.11.e73.

    PubMed 10982554

  • Nabel EG, Plautz G, Nabel GJ. Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science. 1990 Sep 14;249(4974):1285-8. doi: 10.1126/science.2119055.

    PubMed 2119055

  • Schumacher B, Pecher P, von Specht BU, Stegmann T. Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heart disease. Circulation. 1998 Feb 24;97(7):645-50. doi: 10.1161/01.cir.97.7.645.

    PubMed 9495299

  • Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet. 1996 Aug 10;348(9024):370-4. doi: 10.1016/s0140-6736(96)03361-2.

    PubMed 8709735

  • Rosengart TK, Lee LY, Patel SR, Sanborn TA, Parikh M, Bergman GW, Hachamovitch R, Szulc M, Kligfield PD, Okin PM, Hahn RT, Devereux RB, Post MR, Hackett NR, Foster T, Grasso TM, Lesser ML, Isom OW, Crystal RG. Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation. 1999 Aug 3;100(5):468-74. doi: 10.1161/01.cir.100.5.468.

    PubMed 10430759

  • Vale PR, Losordo DW, Milliken CE, McDonald MC, Gravelin LM, Curry CM, Esakof DD, Maysky M, Symes JF, Isner JM. Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia. Circulation. 2001 May 1;103(17):2138-43. doi: 10.1161/01.cir.103.17.2138.

    PubMed 11331253

  • Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999 Aug 6;85(3):221-8. doi: 10.1161/01.res.85.3.221.

    PubMed 10436164

  • Kobayashi T, Hamano K, Li TS, Katoh T, Kobayashi S, Matsuzaki M, Esato K. Enhancement of angiogenesis by the implantation of self bone marrow cells in a rat ischemic heart model. J Surg Res. 2000 Apr;89(2):189-95. doi: 10.1006/jsre.2000.5828.

    PubMed 10729249

  • Tomita S, Mickle DA, Weisel RD, Jia ZQ, Tumiati LC, Allidina Y, Liu P, Li RK. Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg. 2002 Jun;123(6):1132-40. doi: 10.1067/mtc.2002.120716.

    PubMed 12063460

  • Shintani S, Murohara T, Ikeda H, Ueno T, Sasaki K, Duan J, Imaizumi T. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation. 2001 Feb 13;103(6):897-903. doi: 10.1161/01.cir.103.6.897.

    PubMed 11171801

  • Fuchs S, Baffour R, Zhou YF, Shou M, Pierre A, Tio FO, Weissman NJ, Leon MB, Epstein SE, Kornowski R. Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. J Am Coll Cardiol. 2001 May;37(6):1726-32. doi: 10.1016/s0735-1097(01)01200-1.

    PubMed 11345391

  • Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet. 2003 Jan 4;361(9351):47-9. doi: 10.1016/S0140-6736(03)12111-3.

    PubMed 12517468

  • Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature. 2001 Apr 5;410(6829):701-5. doi: 10.1038/35070587.

    PubMed 11287958

  • Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Amano K, Iba O, Imada T, Iwasaka T. Improvement of collateral perfusion and regional function by implantation of peripheral blood mononuclear cells into ischemic hibernating myocardium. Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1804-10. doi: 10.1161/01.atv.0000039168.95670.b9.

    PubMed 12426208

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mononuclear bone marrow derived cells in people with Refractory Angina, run by IRCCS San Raffaele at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 2 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of major adverse cardiac events (MACE), defined as a combined endpoint of death, acute MI (Q-wave and non-Q wave), revascularization procedures and peri-procedural complications. (time frame: 1, 6, 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00820586, which also lists 35 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2012.

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