Cortisone or Drug Eluting Stents (DES) as Compared to Bare Metal Stents (BMS) to EliminAte Restenosis

NCT ID: NCT00369356

Last Updated: 2013-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 375 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2011-01-31

Brief Summary

The possibility of using the new drug eluting stents (DES) technology has significantly changed the mid-term outcome of percutaneous coronary interventions (PCI) in terms of reduced recurrence of angina. The way interventionalists accomplish their work is changing accordingly, with a strong trend to a wider use of DES and a consequent perceived patients' clinical benefit.

Evidences supporting the superiority of DES in reducing ischemic recurrence after PCI compared to traditional stents (BMS) are available from randomized studies. A recent meta-analyses underlines that:

DES are superior to BMS in reducing clinical recurrence of ischemia, DES and BMS offer identical results in terms of death and infarction, Rapamycin and paclitaxel DES offer similar results.

The aim of our study is to perform a multicenter, randomized study to assess the clinical efficacy and safety of the oral prednisone therapy after PCI as a possible systemic alternative to currently available BMS and DES. Furthermore, the study aims at analyzing the clinical outcome of the commercially available DES in the context of an independent research and a cost-benefit comparison with BMS and oral steroids.

Detailed Description

Design of the study

It is very important to underline that this is a "spontaneous" study, i.e. not receiving sponsorship from pharmaceutical industries, stent manufacturers, or any other financial source. This independence from economic interests would contribute to exclude conflicts of interest that may bias the results of the study that is aimed at testing the applicability and the clinical efficacy of this therapy. Furthermore, the assessment of the DES in public hospitals, and beyond the spectrum of the industry-supported studies may offer interesting results of the real life use of these devices.

One of the purposes of the study is a cost-effectiveness analysis. Centers participating in the study should therefore perform PCI according to their common practice with no interference in their decision-making process or technical approach to PCI because of the inclusion of the patients into a randomized study; this is aimed at obtaining an as real as possible situation of the daily practice. Being an spontaneous research, neither a fee will be provided for the enrollment of patients, nor free stents will be given.

The allocation of patients into a BMS or DES treatment will be decided by randomization, and the stents implanted will be selected according to the operator's preference.

The study will include three different groups of patients:

• Control group: receiving BMS;
• DES group: receiving DES;
• Prednisone group: receiving BMS and oral prednisone

Principal objective of the study: is the comparison of the primary endpoint obtained in a control group of patients treated with BMS versus two alternative study groups:

• DES
• BMS and oral prednisone All assuming a similar adjunctive conventional medical treatment.

Secondary endpoint of the study are:

• cost-effectiveness analysis. This will be calculated considering all patients enrolled in the study and analyzed after one year of the treatment. The analysis will take into account the procedural cost of the PCI material, the cost of the medical treatment in the first year of follow-up and the number of event-free days at follow-up. The cost-efficacy analysis will be obtained from the ratio between the cost of the event-free day of follow-up and the possibility of MACE considered in the primary endpoint of the study.
• comparison of the angiographic results. This will be calculated in all patients enrolled.

Conditions

Coronary Artery Disease; Ischemic Heart Disease; Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Bare Metal Stenting

Group Type: SHAM_COMPARATOR

Bare metal coronary stent

Intervention Type: DEVICE

Stenting with BMS only

2

Stenting with DES

Group Type: ACTIVE_COMPARATOR

Drug eluting coronary stent

Intervention Type: DEVICE

Stenting with DES (Cypher or Taxus)

3

Bare metal stenting and administration of prednisone

Group Type: EXPERIMENTAL

Prednisone

Intervention Type: DRUG

Bare metal stenting with administration of oral prednisone as described in the protocol

Interventions

Prednisone

Bare metal stenting with administration of oral prednisone as described in the protocol

Intervention Type: DRUG

Drug eluting coronary stent

Stenting with DES (Cypher or Taxus)

Intervention Type: DEVICE

Bare metal coronary stent

Stenting with BMS only

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patients with diagnosed CAD (either SVD or MVD) with signs or symptoms of myocardial ischemia, scheduled for percutaneous revascularization are all candidates.
• Either native vessels and SVG can be included with de-novo or recurrent lesions.
• Lesions causing a diameter stenosis >50% in a main coronary artery (LAD, RCA, LCx) or their principal branches (Dg, OM, PL, PDA).

Exclusion Criteria

• Diabetes
• Age over 80 years old
• Recent Q wave myocardial infarction (less than 2 weeks)
• Severe hypertension, uncontrolled despite medical treatment
• Gastric ulcer or symptomatic gastritis
• Neoplasia
• Renal failure (creatinine >2.5)
• Left main disease, or left main equivalent (proximal LAD and proximal LCx), or three vessel disease involving the proximal segments of the 3 main coronary branches
• Suboptimal angiographic result of PCI (DS% >30% or TIMI flow <grade 3)
• Contraindications to high-doses of steroids (immunosuppression, active infective disease, osteoporosis, recent use of high doses of steroids).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regione Piemonte

OTHER

Sponsor Role: collaborator

Universita di Verona

OTHER

Sponsor Role: lead

Responsible Party

Flavio Ribichini

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Corrado Vassanelli, MD

Role: STUDY_CHAIR

Università di Verona

Flavio Ribichini, MD

Role: STUDY_DIRECTOR

Università di Verona

Valeria Ferrero, MD

Role: PRINCIPAL_INVESTIGATOR

Università di Verona

Locations

Istituto Clinico Humanitas

Milan, Milano, Italy

Ospedale Maggiore della Carità

Novara, Novara, Italy

European Hospital

Rome, Rome, Italy

Ospedale San Giovanni Bosco

Torino, Torino, Italy

Università di Verona

Verona, Verona, Italy

Countries

Italy

References

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Reference Type: BACKGROUND

PMID: 12475452 (View on PubMed)

Ribichini F, Ferrero V, Agostini M, Vassanelli C. Immunosuppression against restenosis. Efficacy of a radiofrequency guidewire and oral prednisone in achieving and maintaining coronary artery patency after stenting. Cardiovasc Revasc Med. 2005 Jul-Sep;6(3):124-5. doi: 10.1016/j.carrev.2005.08.006. No abstract available.

Reference Type: BACKGROUND

PMID: 16275609 (View on PubMed)

Ferrero V, Ribichini F, Rognoni A, Marino P, Brunelleschi S, Vassanelli C. Comparison of efficacy and safety of lower-dose to higher-dose oral prednisone after percutaneous coronary interventions (the IMPRESS-LD study). Am J Cardiol. 2007 Apr 15;99(8):1082-6. doi: 10.1016/j.amjcard.2006.11.064. Epub 2007 Mar 6.

Reference Type: BACKGROUND

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Ribichini F, Ferrero V, Rognoni A, Marino P, Brunelleschi S, Vassanelli C. Percutaneous treatment of coronary bifurcations: lesion preparation before provisional bare metal stenting and subsequent immunosuppression with oral prednisone. The IMPRESS-Y study. J Interv Cardiol. 2007 Apr;20(2):114-21. doi: 10.1111/j.1540-8183.2007.00250.x.

Reference Type: BACKGROUND

PMID: 17391219 (View on PubMed)

Ribichini F, Tomai F, Paloscia L, Di Sciascio G, Carosio G, Romano M, Verna E, Galli M, Tamburino C, De Cesare N, Pirisi R, Piscione F, Lanteri G, Ferrero V, Vassanelli C; DESIRE investigators. Steroid-eluting stents in patients with acute coronary syndrome: the dexamethasone eluting stent Italian registry. Heart. 2007 May;93(5):598-600. doi: 10.1136/hrt.2006.098467. Epub 2006 Sep 27.

Reference Type: BACKGROUND

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Ribichini F, Joner M, Ferrero V, Finn AV, Crimins J, Nakazawa G, Acampado E, Kolodgie FD, Vassanelli C, Virmani R. Effects of oral prednisone after stenting in a rabbit model of established atherosclerosis. J Am Coll Cardiol. 2007 Jul 10;50(2):176-85. doi: 10.1016/j.jacc.2007.03.031. Epub 2007 Jun 22.

Reference Type: BACKGROUND

PMID: 17616304 (View on PubMed)

Ferrero V, Ribichini F, Pesarini G, Brunelleschi S, Vassanelli C. Glucocorticoids in the prevention of restenosis after coronary angioplasty: therapeutic potential. Drugs. 2007;67(9):1243-55. doi: 10.2165/00003495-200767090-00001.

Reference Type: BACKGROUND

PMID: 17547469 (View on PubMed)

Ribichini F, Tomai F, De Luca G, Boccuzzi G, Presbitero P, Pesarini G, Ferrero V, Ghini AS, Abukaresh R, Aurigemma C, De Luca L, Zavalloni D, Soregaroli D, Marino P, Garbo R, Zanolla L, Vassanelli C; CEREA-DES investigators. Immunosuppressive therapy with oral prednisone to prevent restenosis after PCI. A multicenter randomized trial. Am J Med. 2011 May;124(5):434-43. doi: 10.1016/j.amjmed.2010.11.027.

Reference Type: RESULT

PMID: 21531233 (View on PubMed)

Ribichini F, Tomai F, Pesarini G, Zivelonghi C, Rognoni A, De Luca G, Boccuzzi G, Presbitero P, Ferrero V, Ghini AS, Marino P, Vassanelli C; CEREA-DES Investigators. Long-term clinical follow-up of the multicentre, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: Cortisone plus BMS or DES veRsus BMS alone to EliminAte Restenosis (CEREA-DES). Eur Heart J. 2013 Jun;34(23):1740-8. doi: 10.1093/eurheartj/eht079. Epub 2013 Mar 14.

Reference Type: DERIVED

PMID: 23492671 (View on PubMed)

Ribichini F, Tomai F, De Luca G, Boccuzzi G, Presbitero P, Pesarini G, Ferrero V, Ghini AS, Pastori F, De Luca L, Zavalloni D, Soregaroli D, Garbo R, Franchi E, Marino P, Minelli M, Vassanelli C. A multicenter, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: cortisone plus BMS or DES versus BMS alone to eliminate restenosis (CEREA-DES) - study design and rationale. J Cardiovasc Med (Hagerstown). 2009 Feb;10(2):192-9. doi: 10.2459/JCM.0b013e32831f9176.

Reference Type: DERIVED

PMID: 19377384 (View on PubMed)

Other Identifiers

CEREA-DES

Identifier Type: -

Identifier Source: org_study_id