Optical Coherence Tomography Assessment of Gender diVersity In Primary Angioplasty. The OCTAVIA Trial (OCTAVIA)

• ClinicalTrials.gov Identifier: NCT01377207
• Recruitment Status: Completed
• First Posted: June 21, 2011
• Last Update Posted: April 19, 2013
• Sponsor: Italian Society of Invasive Cardiology
• Collaborator: Meditrial SrL
• Information provided by (Responsible Party): Italian Society of Invasive Cardiology

Study Description

Brief Summary:

Recent studies suggest important gender differences in the pathophysiology and prognosis of ST-segment elevation myocardial infarction (STEMI). This is the first prospective controlled study to assess gender differences in the mechanism of plaque rupture/erosion and thrombus formation in patients presenting with STEMI treated with primary angioplasty. Gender-related mechanisms of plaque rupture or erosion will be investigated using a combination of Quantitative Coronary Angiography, high resolution Optical Coherence Tomography of the culprit vessel and histopathologic analyses of thrombus aspirates of the infarct related lesion, performed by independent core laboratories, blinded to group (male or female) and clinical variables.

Condition or disease	Intervention/treatment	Phase
Acute Myocardial Infarction	Procedure: Primary PCI	Phase 4

Detailed Description:

In OCTAVIA; enrollment in a 1:1 ratio according to gender group will be ensured by a computer-assisted matching algorithm for gender and age (< 50, 51-70, and > 70 years). Matching has the purpose to enable enrollment of an even number of male and female patients in balanced age groups. This type of dynamic algorithm is appropriate when the composition of the referral population is not known in advance.

OCTAVIA will assess gender differences in the mechanism of plaque rupture. The study will also evaluate the changes in the vascular territory remote from the infarct related lesion, the local vascular response to primary angioplasty interventions and the correlation with clinical outcomes over one year of follow-up. These data are important to support a gender based differential strategy and can have a substantial impact for the improvement of clinical practice in the treatment of women with STEMI.

The study sample of 140 patients is sized to address the hypothesis that the female population has a lower prevalence of plaque rupture (primary endpoint) at baseline OCT than the male population. Computations were conducted assuming a prevalence of rupture of 82% in males and 60% in female patients (22% lower).

Confirmatory power calculation was performed on the basis of stent Strut Coverage at 9 month follow-up (co primary endpoint). Stent-strut coverage and apposition have been linked to the risk of stent thrombosis. However, our understanding of DES healing in male and female patients with ST-segment elevation myocardial infarction is restricted to post-mortem data. The investigators assumed a per patient stent strut coverage (a continuous variable with right skewed distribution) with mean of 97.0% and standard deviation of 4.0% in men, versus mean of 95.0% and standard deviation of 4.0% in women, following Xience Prime implantation. Thus, aiming for a 5% 2-tailed superiority alpha, an 80% power, and assuming a 1:1 enrollment according to gender, a total of 64 patients per group should be enrolled. Anticipating a 10% dropout rate due to patients lost to follow-up and inadequate imaging (included major side branch sections), the total enrollment is set at 70 patients per group (total population of 140 subjects).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Optical Coherence Tomography Assessment of Gender diVersity In Primary Angioplasty. The OCTAVIA Trial
• Study Start Date: January 2011
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: April 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Female Arm; Female gender diagnosed with ST segment Elevation Myocardial Infarction (STEMI)	Procedure: Primary PCI; Thrombus aspiration and hystopathological analysis, Optical Coherence Tomography assessment of STEMI culprit vessel, Primary PCI with Drug Eluting Stent implantation; Repeat OCT assessment of culprit vessel at 9 monts follow-up
Active Comparator: Male Arm; Male Gender diagnosed with ST segment Elevation Acute Myocardial Infarction (STEMI)	Procedure: Primary PCI; Thrombus aspiration and hystopathological analysis, Optical Coherence Tomography assessment of STEMI culprit vessel, Primary PCI with Drug Eluting Stent implantation; Repeat OCT assessment of culprit vessel at 9 monts follow-up

Outcome Measures

Primary Outcome Measures :

1. Percentage of ruptured or eroded plaques at infarct related lesion as assessed by OCT before PCI [ Time Frame: Plaque rupture is evaluated during the index PCI procedure. ]
   To assess gender differences in the percentage of ruptured or eroded plaques at infarct related lesion as assessed by OCT. The OCT measurement is taken before stenting, when a TIMI flow 2-3 is detected. If baseline flow is TIMI 1, thrombus aspiration is performed before OCT.
2. Percent of covered stent struts by OCT in infarct-related lesion at 9 months (co-primary endpoint). [ Time Frame: Stent coverage is evaluated at 9 months by OCT performed in all patients. ]
   To assess gender differences in the percentage of covered stent struts at infarct related lesion as assessed by OCT performed in all patients at 9 months.

Secondary Outcome Measures :

1. Minimal Fibrous Cap Thickness (MFCA) (µm) at infarct-related lesion as determined by OCT. [ Time Frame: MFCA at index procedure (immediately after reestablishment of TIMI 2-3 coronary flow by PCI) and at 9 months OCT performed in all patients. ]

   To assess gender differences in Minimal Fibrous Cap Thickness at infart related lesion by OCT immediataly after reestablishment of TIMI (Thrombolysis In Myocardial Infarction) 2-3 coronary blood flow and before stent implantation.

   The evolution of fibrous cap thickness over time will be determined by OCT that will be performed in all patients at 9 months from the index procedure.

2. Presence and type of residual thrombus material in the culprit vessel. [ Time Frame: Residual thrombus in the infarct related vessel is evaluated during the index procedure: immediately after reestablishment of TIMI 2-3 coronary flow during primary percutaneous coronary intervention ]
   To assess gender differences in thrombus type by OCT in culprit vessel after reestablishment of TIMI (Thrombolysis In Myocardial Infarction) 2-3 coronary blood flow and before stent implantation.
3. Number of TCFA (<65 µM) as assessed by OCT in the culprit vessel (infarct related). [ Time Frame: Thin Fibrous Cap Atheroma is assessed during the index procedure: immediately after reestablishment of TIMI 2-3 coronary flow before stent implantationduring PCI; and at 9 months by OCT performed in all patients. ]
   To assess gender difference in TCFA number as assessed by OCT in the infarct related vessel during the index procedure and at 9 months by OCT performed in all patients
4. percent of malapposed-uncovered struts [ Time Frame: 9 months ]
   to assess gender difference in % malapposed/uncovered struts at 9 months follow up by OCT
5. percent net volume obstruction [ Time Frame: 9 months ]
   To assess gender difference in % of stent volume obstruction by OCT at 9 months follow up
6. percent abnormal intraluminal tissue [ Time Frame: 9 months ]
   To assess gender difference in % of abnormal intraluminal tissue by OCT at 9 months follow up

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Acute Myocardial MI with ST segment Elevation, within 6 hours from symptoms onset
• Native coronary artery disease (no prior stent implant, no prior brachytherapy)
• Signed patient informed consent

Exclusion Criteria:

• Patients with left main disease
• infarct lesions in bypass grafts
• cardiogenic shock
• renal failure
• recent major bleeding
• allergy to aspirin or clopidogrel
• on anticoagulant therapy
• no suitable anatomy for OCT (extreme tortuousity, very distal culprit lesion, and large infarct vessel > 4 mm in diameter)

Contacts and Locations

Locations

Italy

Ospedale Cardinal Massai

Asti, AT, Italy, 14100

Ospedali Riuniti di Bergamo

Bergamo, BG, Italy, 24124

Policlinico S.Orsola- Malpighi

Bologna, BO, Italy

Ospedale Ferrarotto

Catania, CT, Italy

Ospedale S. Anna

Ferrara, FE, Italy, 44100

USL 9 Grosseto

Grosseto, GR, Italy, 48100

Policlinico Padova

Padova, PD, Italy

Policlinico Parma

Parma, PR, Italy, 43126

Policlinico Le Scotte

Siena, SI, Italy, 53100

Ospedale San Giovanni Bosco

Torino, TO, Italy, 10154

Ospedale Le Molinette

Torino, TO, Italy

Ospedale Mauriziano

Torino, TO, Italy

Ospedale Civile

Mirano, VE, Italy

Policlinico Gemelli

Rome, Italy, 00168

Sponsors and Collaborators

Italian Society of Invasive Cardiology

Meditrial SrL

Investigators

• Principal Investigator: Giulio Guagliumi, MD; Italian Society of Invasive Cardiology

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Saia F, Komukai K, Capodanno D, Sirbu V, Musumeci G, Boccuzzi G, Tarantini G, Fineschi M, Tumminello G, Bernelli C, Niccoli G, Coccato M, Bordoni B, Bezerra H, Biondi-Zoccai G, Virmani R, Guagliumi G; OCTAVIA Investigators. Eroded Versus Ruptured Plaques at the Culprit Site of STEMI: In Vivo Pathophysiological Features and Response to Primary PCI. JACC Cardiovasc Imaging. 2015 May;8(5):566-575. doi: 10.1016/j.jcmg.2015.01.018. Epub 2015 Apr 15.

Guagliumi G, Capodanno D, Saia F, Musumeci G, Tarantini G, Garbo R, Tumminello G, Sirbu V, Coccato M, Fineschi M, Trani C, De Benedictis M, Limbruno U, De Luca L, Niccoli G, Bezerra H, Ladich E, Costa M, Biondi Zoccai G, Virmani R; OCTAVIA Trial Investigators. Mechanisms of atherothrombosis and vascular response to primary percutaneous coronary intervention in women versus men with acute myocardial infarction: results of the OCTAVIA study. JACC Cardiovasc Interv. 2014 Sep;7(9):958-68. doi: 10.1016/j.jcin.2014.05.011. Epub 2014 Aug 13.

• Responsible Party: Italian Society of Invasive Cardiology
• ClinicalTrials.gov Identifier: NCT01377207
• Other Study ID Numbers: 27/01/2011
• First Posted: June 21, 2011
• Last Update Posted: April 19, 2013
• Last Verified: April 2013

Keywords provided by Italian Society of Invasive Cardiology:

ST segment Elevation Myocardial Infarction; Optical Coherence Tomography; Percutaneous Coronary Intervention; Thrombus hystopathology; Gender differences

Additional relevant MeSH terms:

Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases