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Acute Myocardial InfarctionPhase 3CYCLENCT01650662

CYCLosporinE A in Reperfused Acute Myocardial Infarction

A Phase 3 study testing Cyclosporine A in people with Acute Myocardial Infarction, run by Mario Negri Institute for Pharmacological Research at 31 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myocardial Infarction
What is being tested?
Cyclosporine A
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
410 participants
Where
31 sitesItaly
Study dates
Jan 2012to Oct 2014
Phase
Phase 3
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

Italy31 sites

  • Ospedale Regionale Umberto Parini

    Aosta, AO, 11100

  • Ospedale S. Donato

    Arezzo, AR, 52100

  • Ospedale San Paolo

    Bari, BA, 70100

  • Ospedale Maggiore

    Bologna, BO, 40100

  • Istituto Fondazione Poliambulanza

    Brescia, BS, 25100

  • Azienda Ospedaliera G.Brotzu

    Cagliari, CA, 09100

  • Ospedale S. Giacomo

    Castelfranco Veneto, TV, 31033

  • Azienda Ospedaliera Santa Croce e Carle

    Cuneo, CN, 12100

  • Ospedale di Desio

    Desio, MB, 20832

  • Ospedale G.B. Morgani - L. Pierantoni

    Forlì, Forli, 47100

  • Ospedale delle Misericordie

    Grosseto, GR, 58100

  • Ospedale Campo di Marte

    Lucca, LU, 55100

  • Ospedale dell'Angelo

    Mestre, VE, 30100

  • Policlinico Monza

    Monza, MB, 20900

  • AOR Villa Sofia - Cervello P.O.

    Palermo, PA, 90100

  • AOR Villa Sofia - Cervello PO Villa Sofia

    Palermo, PA, 90100

  • Ospedale Civile dello Spirito Santo

    Pescara, PE, 65100

  • Ospedale Santa Corona

    Pietra Ligure, SV, 17027

  • Ospedale Santa Maria delle Croci

    Ravenna, RA, 48100

  • Ospedale Infermi

    Rimini, RN, 47921

  • Ospedale degli Infermi

    Rivoli, TO, 10098

  • Ospedale San Camillo

    Roma, RM, 00100

  • Azienda Ospedaliera di Seriate

    Seriate, BG, 24068

  • Ospedale Maria Vittoria

    Torino, TO, 10100

  • Ospedale Santa Chiara

    Trento, TN, 38100

  • Azienda Ospedaliera di Treviglio

    Treviglio, BG, 24047

  • Ospedale Ca' Foncello

    Treviso, TV, 31100

  • Azienda Ospedaliera Universitaria - Ospedale Riuniti

    Trieste, TS, 34121

  • Azienda Ospedaliera -Univ. S. Maria delle Misericordie

    Udine, UD, 33200

  • Ospedale Civile San Bortolo

    Vicenza, VI, 36100

  • Policlinico S.Marco

    Zingonia - Osio Sotto, BG, 24040

Other trials in Italy

About this study

Official title: CYCLosporinE A in Reperfused Acute Myocardial Infarction Prospective, Controlled, Randomized, Multicentre Trial to Examine Whether a Single i.v. Bolus of Cyclosporine A Before PCI Can Reduce Myocardial Reperfusion Injury in Patients With STEMI.

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.

Read the detailed description

The possibility of optimizing the results of an early and effective reopening of the occluded artery by reducing/avoiding the impact of the so-called reperfusion injury has been for many years one of the most elusive objectives of pharmacological research, with evolving hypothesis and targets.

A recently published trial has provided support to a line of investigation focused on the role of mitochondrial dysfunction, the so-called permeability transition, as cause of irreversible myocardial injury associated to reperfusion. In fact, a single dose of the widely used immunosuppressant agent, CsA, a potent inhibitor of mitochondrial permeability transition pore opening, was reported to limit ischemia-reperfusion injury in 50 patients with anterior MI who underwent primary PCI.

Since infarct size and left ventricular function are the main determinants of long-term morbidity and mortality, a single measure to limit infarct size is of potential clinical benefit. Therefore the results of the previously mentioned trial should be replicated in a larger sample size, before going on to a trial with clinical endpoints.

  • Sample size

Assuming an incidence of the primary endpoint of 55% in the control group, we calculated that 444 patients (222 patients per group) will be required for the study to have 80% power to detect a 25% relative improvement (resulting in an endpoint frequency of 68.7% in the CsA group) with a 5% drop-out rate and a two-sided alpha level of 5%. The size of the trial will allow to investigate treatment benefit for the secondary endpoint hsTnT: assuming a concentration of 2.7 ng/mL on day 4 (common SD=2.1) in the control group, the study will have a 90% power to show a 25% reduction with CsA at a two-sided alpha level of 5%.

  • Safety

Adverse events with intravenous CsA (i.e. anaphylactoid reactions/anaphylactic shock, acute renal failure, or hypertensive crisis) are reported to be very rare. In this trial, patients will receive only one iv dose of CsA, therefore we expect a low probability of adverse effects related to repeated administrations, i.e. acute renal failure or hypertensive crisis. Nonetheless a close monitoring of the safety of the single dose of CsA is foreseen with monthly examination of data of safety by the Steering Committee.

Being tested
Cyclosporine A
Keywords
Acute Myocardial Infarction, Cyclosporine A, Reperfusion, Clinical Trial

What participants receive

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

  • Cyclosporine ADrug

    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.

Study groups in NCT01650662
Study groupRoleWhat they receive
Cyclosporine AExperimentalThe 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.
Receives: Drug: Cyclosporine A
Control groupExperimentalThe control group received on the top of recommended standard care for acute myocardial infarction.
Receives: Drug: Cyclosporine A

What is being measured

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

  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

    Measured: 1 hour after percutaneous coronary intervention (PCI)

Secondary outcomes (5)

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

    High sensitive cardiac troponin T (hs-cTnt) at day 4 after PCI; ; this will be the most relevant among secondary endpoints given its value as readout of cardiac protection.

    Measured: at day 4 after percutaneous coronary intervention (PCI)

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

    Clinical events within 6 months of randomization: all-cause mortality, HF or shock; rehospitalization for CV reasons.

    Measured: within 6 months of randomization

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

    Infarct size: Troponin curve (T or I, assayed locally); The time course of troponin release during the first 72 hours after the visualization of the antegrade flow, will be studied.

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

  4. LV remodeling and function as assessed by echocardiography;

    LV remodeling and function at 6 months, as assessed by echocardiography;

    Measured: at 6 months after randomization

  5. No reflow, as assessed by myocardial blush

    No reflow, as assessed by myocardial blush after the visualization of the antegrade flow

    Measured: 1 day (after the visualization of the antegrade flow)

Timeline

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

  1. First posted26 Jul 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionOct 2014
  4. Study completionOct 2014

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
410 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01650662
Sponsor's protocol ID
CYCLE (IRFMN_5635)
Other IDs
2011-002876-18
Acronym
CYCLE
Status last verified
Oct 2013
First submitted
24 Jul 2012
Last updated
16 Apr 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 26821623

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cyclosporine A in people with Acute Myocardial Infarction, run by Mario Negri Institute for Pharmacological Research at 31 sites 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 8 inclusion and 12 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: finished, as of the sponsor's last update on 16 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Improvement of myocardial reperfusion, measured with ST-segment resolution >=70% (time frame: 1 hour after percutaneous coronary intervention (PCI)). 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 NCT01650662, which also lists 1 linked publication.

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 16 Apr 2015.

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