The Effect of Glucocorticoid Therapy on Left Ventricular Remodelling in Acute Myocardial Infarction (RECONSIDER)

NCT03371784 | Unknown Phase 2

• 1 other identifier: PN-III-P4-ID-PCE-2016-0393
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: In the setting of acute ST-segment elevation myocardial infarction (STEMI) coronary wedge pressure (CWP) emerges as a new marker for the advanced form of pre-procedural microvascular obstruction (MVO), which is associated with inflammatory interstitial edema. Through its anti-inflammatory effects, glucocorticoid therapy may prove beneficial in patients with high CWP. Aim: To identify the presence of the advanced form of MVO before primary percutaneous coronary intervention (PPCI) by CWP measurement and to test the benefit of cortisol therapy, in terms of infarct size and left ventricular remodeling, in patients with raised CWP. Methods: 50 patients with a first STEMI, candidates for PPCI, with proximal coronary occlusion, will undergo CWP measurement followed by percutaneous revascularization. Cardiac MRI will be performed 3-5 days after the procedure. A cutoff for CWP in predicting MVO, interstitial oedema and intramyocardial haemorrhage will be derived.Based on the above mentioned cutoff, 180 patients with continuous elevation of the pressure line will be randomized, by a 1:1 model, either to cortisol therapy or to placebo. Inflammatory parameters will be determined from peripheral blood samples. Patients will undergo cardiac magnetic resonance (CMR) imaging 3 to 5 days after revascularization. Study endpoints: The primary endpoint will be the extent of MVO, interstitial edema and hemorrhage. Secondary endpoints will include infarct size, myocardial salvage, left ventricular volumes and ejection fraction. The clinical endpoints of all-cause and cardiovascular death, myocardial re-infarction, target vessel revascularization, stent thrombosis and stroke will be recorded at 6 months.

Conditions

ST-segment Elevation Myocardial Infarction; Left Ventricular Remodeling

Keywords

Acute myocardial infarction; Left ventricular remodeling; Coronary wedge pressure; Glucocorticoid therapy

Outcome Measures

Primary Outcomes (1)

• The extent of interstitial edema

  Cardiac magnetic resonance (CMR) assessment (% of left ventricular end-diastolic mass)

  3-5 days

Secondary Outcomes (7)

• The extent of microvascular obstruction

  3-5 days

• The extent of intramyocardial haemorrhage

  3-5 days

• Infarct size

  3-5 days

• Myocardial salvage

  3-5 days

• Left ventricular ejection fraction

  3-5 days and 6 months after the procedure

Study Arms (2)

Hydrocortisone

ACTIVE COMPARATOR

Patients who meet the inclusion criteria, with a CWP above the derived cutoff, with continuous elevation of the pressure line, who are randomized to i.v hydrocortisone administration.

Drug: Hydrocortisone

Placebo

PLACEBO COMPARATOR

Patients who meet the inclusion criteria, with a CWP above the derived cutoff, with continuous elevation of the pressure line, who are randomized to placebo (sodium chloride 0.9%).

Drug: Placebo

Interventions

Hydrocortisone DRUG

I.V. administration

Also known as: no other name

Hydrocortisone

Placebo DRUG

I.V. administration

Also known as: sodium chloride 0.9%

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age: 18-85 years
• first episode of ST-segment elevation myocardial infarction
• candidates for primary PCI (typical cardiac chest pain, within 12h of symptom onset, with ST-segment elevation of more than 1 mm in at least two contiguous leads)
• left anterior descending artery culprit lesion

You may not qualify if:

• cardiogenic shock
• previous PCI and coronary artery bypass surgery (CABG)
• left bundle branch block
• active bleeding
• administration of thrombolytic agents for the current episode
• recent stroke (during last month)
• indication for oral anticoagulant therapy
• severe or untreated infection
• the impossibility of CWP measurement.

Sponsors & Collaborators

• Iuliu Hatieganu University of Medicine and Pharmacy: lead
• Romanian Governmental Funding (UEFISCDI): collaborator

Study Sites (1)

"Niculae Stancioiu" Heart Institute

Cluj-Napoca, Cluj, 400001, Romania

Location

Related Publications (9)

• Westman PC, Lipinski MJ, Luger D, Waksman R, Bonow RO, Wu E, Epstein SE. Inflammation as a Driver of Adverse Left Ventricular Remodeling After Acute Myocardial Infarction. J Am Coll Cardiol. 2016 May 3;67(17):2050-60. doi: 10.1016/j.jacc.2016.01.073.

  PMID: 27126533 BACKGROUND

• Kramer MC, van der Wal AC, Koch KT, Ploegmakers JP, van der Schaaf RJ, Henriques JP, Baan J Jr, Rittersma SZ, Vis MM, Piek JJ, Tijssen JG, de Winter RJ. Presence of older thrombus is an independent predictor of long-term mortality in patients with ST-elevation myocardial infarction treated with thrombus aspiration during primary percutaneous coronary intervention. Circulation. 2008 Oct 28;118(18):1810-6. doi: 10.1161/CIRCULATIONAHA.108.780734. Epub 2008 Oct 13.

  PMID: 18852369 BACKGROUND

• Patel N, Petraco R, Dall'Armellina E, Kassimis G, De Maria GL, Dawkins S, Lee R, Prendergast BD, Choudhury RP, Forfar JC, Channon KM, Davies J, Banning AP, Kharbanda RK. Zero-Flow Pressure Measured Immediately After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Provides the Best Invasive Index for Predicting the Extent of Myocardial Infarction at 6 Months: An OxAMI Study (Oxford Acute Myocardial Infarction). JACC Cardiovasc Interv. 2015 Sep;8(11):1410-1421. doi: 10.1016/j.jcin.2015.04.029.

  PMID: 26404192 BACKGROUND

• Iancu AC, Rafiroiu D, Marc M. Is Coronary Wedge Pressure a Technique to Identify High-Risk Patients Who May Benefit From Alternative Treatment in Acute Myocardial Infarction?: Is This The Next Step? JACC Cardiovasc Interv. 2016 Jan 11;9(1):104-105. doi: 10.1016/j.jcin.2015.10.018. No abstract available.

  PMID: 26762918 BACKGROUND

• Ndrepepa G, Tiroch K, Fusaro M, Keta D, Seyfarth M, Byrne RA, Pache J, Alger P, Mehilli J, Schomig A, Kastrati A. 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol. 2010 May 25;55(21):2383-9. doi: 10.1016/j.jacc.2009.12.054.

  PMID: 20488311 BACKGROUND

• Iancu A, Ober C, Bondor CI, Cadis H. Microvascular effect of intracoronary eptifibatide in acute myocardial infarction. Cardiology. 2012;123(1):46-53. doi: 10.1159/000341197. Epub 2012 Sep 12.

  PMID: 22986471 BACKGROUND

• Giugliano GR, Giugliano RP, Gibson CM, Kuntz RE. Meta-analysis of corticosteroid treatment in acute myocardial infarction. Am J Cardiol. 2003 May 1;91(9):1055-9. doi: 10.1016/s0002-9149(03)00148-6.

  PMID: 12714146 BACKGROUND

• Barzilai D, Plavnick J, Hazani A, Einath R, Kleinhaus N, Kanter Y. Use of hydrocortisone in the treatment of acute myocardial infarction. Summary of a clinical trial in 446 patients. Chest. 1972 May;61(5):488-91. doi: 10.1378/chest.61.5.488. No abstract available.

  PMID: 5046847 BACKGROUND

• Seropian IM, Toldo S, Van Tassell BW, Abbate A. Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. J Am Coll Cardiol. 2014 Apr 29;63(16):1593-603. doi: 10.1016/j.jacc.2014.01.014. Epub 2014 Feb 13.

  PMID: 24530674 BACKGROUND

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Ventricular Remodeling

Interventions

Hydrocortisone; Sodium Chloride

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Adrian Corneliu Iancu, M.D, Ph.D

  "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology

Model Details: 1:1 model randomization

Study Record Dates

• First Submitted: December 4, 2017
• First Posted: December 13, 2017
• Study Start: March 8, 2018
• Primary Completion: December 31, 2019
• Study Completion: December 1, 2020
• Last Updated: September 28, 2020

Record last verified: 2020-09

Locations

RO (1)