CYCLosporinE A in Reperfused Acute Myocardial Infarction

NCT01650662 | Completed Phase 3 DMC

• 2 other identifiers: CYCLE (IRFMN_5635)2011-002876-18
• Study Type: interventional
• Target: 410
• Locations: 1 country
• Sites: 31

Brief Summary

Infarct size is a major determinant of prognosis after myocardial infarction (MI). It has been reported that Cyclosporine A (CsA) administered immediately prior to percutaneous coronary intervention (PCI) significantly could reduce reperfusion injury and consequently infarct size in ST elevation MI (STEMI) patients. CYCLE trial is a multicenter, controlled, randomized open label study, with blind assessment of endpoint measures. The objective is to determine whether a single i.v. dose of CsA within 6 hour onset of symptoms of STEMI in 444 patients, improves outcomes after successful primary PCI, by reducing myocardial injury associated to reperfusion.

Conditions

Acute Myocardial Infarction

Keywords

Acute Myocardial Infarction; Cyclosporine A; Reperfusion; Clinical Trial

Outcome Measures

Primary Outcomes (1)

• Improvement of myocardial reperfusion, measured with ST-segment resolution >=70%

  Improvement of myocardial reperfusion, measured with ST-segment resolution \>=70% 1 hour after PCI

  1 hour after percutaneous coronary intervention (PCI)

Secondary Outcomes (5)

• High sensitive cardiac troponin T (hs-cTnt).

  at day 4 after percutaneous coronary intervention (PCI)

• Clinical events: all-cause mortality, HF or shock; rehospitalization for CV reasons

  within 6 months of randomization

• Infarct size: Troponin curve (T or I, assayed locally)

  Time course of troponin release during the first 72 hours after the visualization of the antegrade flow.

• LV remodeling and function as assessed by echocardiography;

  at 6 months after randomization

• No reflow, as assessed by myocardial blush

  1 day (after the visualization of the antegrade flow)

Study Arms (2)

Cyclosporine A

EXPERIMENTAL

The investigational active treatment is CsA, an immunosuppressant indicated for the prevention of acute rejection after organ transplant, including cardiac transplantation. The preparation used in the trial will be Sandimmun IV, containing CsA 50 mg/ml, Cremophor® EL and 94% ethyl alcohol in a 5 ml vial. Patients will received Cyclosporine A on the top of recommended standard care for acute myocardial infarction.

Drug: Cyclosporine A

Control group

EXPERIMENTAL

The control group received on the top of recommended standard care for acute myocardial infarction.

Drug: Cyclosporine A

Interventions

Cyclosporine A DRUG

In the CsA group, at least 5 min before balloon inflation and stenting, patients will receive an intravenous bolus injection of 2.5 mg/kg of CsA. In the control group, patients will receive only recommended treatments. CsA will be dissolved in normal NaCl 0.9% solution (final concentration 25 mg/ml) and injected slowly (over 20-30 seconds) via a catheter positioned in an antecubital vein at least 5 min before PCI, to allow for distribution of the drug.

Control group; Cyclosporine A

Eligibility Criteria

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

You may qualify if:

• Male and female patients with large STEMI not older than 6 hours, defined as
• angina pectoris or equivalent symptoms of more than 20 minutes duration within last 6 hours, and
• ST elevation in at least 3 leads in anterior MI and/or a deviation in at least 4 leads in inferior MI,
• TIMI flow 0 or 1 in identified culprit artery
• Intended acute primary PCI
• Age ≥ 18 years
• Ability to understand the nature, scope, and possible consequences of the study participation/legal capacity
• Written informed consent

You may not qualify if:

• Left bundle branch block
• TIMI flow \> 1 in the identified culprit artery
• Treatment with CsA within last 10 days
• Contraindication to CsA or history of allergic reaction to CsA
• Coronary anatomy not suitable for PCI
• Thrombolytic therapy within 24 h. before randomization
• Previous MI
• Previous CABG
• Severe renal or hepatic insufficiency
• Malignant tumor, not curatively treated
• Women with childbearing potential, esp. pregnant or nursing women
• Participation in another clinical or device trial within the previous 30 days

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Heart Care Foundation: collaborator

Study Sites (31)

Ospedale Regionale Umberto Parini

Aosta, AO, 11100, Italy

Location

Ospedale S. Donato

Arezzo, AR, 52100, Italy

Location

Ospedale San Paolo

Bari, BA, 70100, Italy

Location

Azienda Ospedaliera di Seriate

Seriate, BG, 24068, Italy

Location

Azienda Ospedaliera di Treviglio

Treviglio, BG, 24047, Italy

Location

Policlinico S.Marco

Zingonia - Osio Sotto, BG, 24040, Italy

Location

Ospedale Maggiore

Bologna, BO, 40100, Italy

Location

Istituto Fondazione Poliambulanza

Brescia, BS, 25100, Italy

Location

Azienda Ospedaliera G.Brotzu

Cagliari, CA, 09100, Italy

Location

Azienda Ospedaliera Santa Croce e Carle

Cuneo, CN, 12100, Italy

Location

Ospedale G.B. Morgani - L. Pierantoni

Forlì, Forli, 47100, Italy

Location

Ospedale delle Misericordie

Grosseto, GR, 58100, Italy

Location

Ospedale Campo di Marte

Lucca, LU, 55100, Italy

Location

Ospedale di Desio

Desio, MB, 20832, Italy

Location

Policlinico Monza

Monza, MB, 20900, Italy

Location

AOR Villa Sofia - Cervello P.O.

Palermo, PA, 90100, Italy

Location

AOR Villa Sofia - Cervello PO Villa Sofia

Palermo, PA, 90100, Italy

Location

Ospedale Civile dello Spirito Santo

Pescara, PE, 65100, Italy

Location

Ospedale Santa Maria delle Croci

Ravenna, RA, 48100, Italy

Location

Ospedale San Camillo

Roma, RM, 00100, Italy

Location

Ospedale Infermi

Rimini, RN, 47921, Italy

Location

Ospedale Santa Corona

Pietra Ligure, SV, 17027, Italy

Location

Ospedale Santa Chiara

Trento, TN, 38100, Italy

Location

Ospedale degli Infermi

Rivoli, TO, 10098, Italy

Location

Ospedale Maria Vittoria

Torino, TO, 10100, Italy

Location

Azienda Ospedaliera Universitaria - Ospedale Riuniti

Trieste, TS, 34121, Italy

Location

Ospedale S. Giacomo

Castelfranco Veneto, TV, 31033, Italy

Location

Ospedale Ca' Foncello

Treviso, TV, 31100, Italy

Location

Azienda Ospedaliera -Univ. S. Maria delle Misericordie

Udine, UD, 33200, Italy

Location

Ospedale dell'Angelo

Mestre, VE, 30100, Italy

Location

Ospedale Civile San Bortolo

Vicenza, VI, 36100, Italy

Location

Related Publications (1)

• Ottani F, Latini R, Staszewsky L, La Vecchia L, Locuratolo N, Sicuro M, Masson S, Barlera S, Milani V, Lombardi M, Costalunga A, Mollichelli N, Santarelli A, De Cesare N, Sganzerla P, Boi A, Maggioni AP, Limbruno U; CYCLE Investigators. Cyclosporine A in Reperfused Myocardial Infarction: The Multicenter, Controlled, Open-Label CYCLE Trial. J Am Coll Cardiol. 2016 Feb 2;67(4):365-374. doi: 10.1016/j.jacc.2015.10.081.

  PMID: 26821623 DERIVED

Related Links

• The protocol presentation, can be found in the window of CYCLE Study.

MeSH Terms

Interventions

Cyclosporine

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Roberto Latini, MD

  Mario Negri Institute, Milan, Italy

  STUDY CHAIR

• Filippo Ottani, MD

  Ospedale G.B. Morgagni, Pierantoni, Forlì, Italy

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2012
• First Posted: July 26, 2012
• Study Start: January 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: April 16, 2015

Record last verified: 2013-10

Locations

IT (31)