Clinical trial NCT01377207: Optical Coherence Tomography Assessment of Gender diVersity In Primary Angioplasty. The OCTAVIA Trial
Official title: Optical Coherence Tomography Assessment of Gender diVersity In Primary Angioplasty. The OCTAVIA Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Myocardial Infarction
Keywords: ST segment Elevation Myocardial Infarction
Optical Coherence Tomography
Percutaneous Coronary Intervention
Thrombus hystopathology
Gender differences
Lead sponsor: Italian Society of Invasive Cardiology
Sponsor class: OTHER
Collaborators: name: Meditrial SrL
First posted: 2011-06-21
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility 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)

Primary outcomes:
measure: Percentage of ruptured or eroded plaques at infarct related lesion as assessed by OCT before PCI
timeFrame: Plaque rupture is evaluated during the index PCI procedure.
measure: Percent of covered stent struts by OCT in infarct-related lesion at 9 months (co-primary endpoint).
timeFrame: Stent coverage is evaluated at 9 months by OCT performed in all patients.
Secondary outcomes:
measure: Minimal Fibrous Cap Thickness (MFCA) (µm) at infarct-related lesion as determined by OCT.
timeFrame: MFCA at index procedure (immediately after reestablishment of TIMI 2-3 coronary flow by PCI) and at 9 months OCT performed in all patients.
measure: Presence and type of residual thrombus material in the culprit vessel.
timeFrame: 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
measure: Number of TCFA (<65 µM) as assessed by OCT in the culprit vessel (infarct related).
timeFrame: 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.
measure: percent of malapposed-uncovered struts
timeFrame: 9 months
measure: percent net volume obstruction
timeFrame: 9 months
measure: percent abnormal intraluminal tissue
timeFrame: 9 months
Other outcomes:
Locations:
city: Asti
country: Italy
facility: Ospedale Cardinal Massai
state: AT
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
state: BG
city: Bologna
country: Italy
facility: Policlinico S.Orsola- Malpighi
state: BO
city: Catania
country: Italy
facility: Ospedale Ferrarotto
state: CT
city: Ferrara
country: Italy
facility: Ospedale S. Anna
state: FE
city: Grosseto
country: Italy
facility: USL 9 Grosseto
state: GR
city: Padova
country: Italy
facility: Policlinico Padova
state: PD
city: Parma
country: Italy
facility: Policlinico Parma
state: PR
city: Siena
country: Italy
facility: Policlinico Le Scotte
state: SI
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco
state: TO
city: Torino
country: Italy
facility: Ospedale Le Molinette
state: TO
city: Torino
country: Italy
facility: Ospedale Mauriziano
state: TO
city: Mirano
country: Italy
facility: Ospedale Civile
state: VE
city: Rome
country: Italy
facility: Policlinico Gemelli
Study officials:
affiliation: Italian Society of Invasive Cardiology
name: Giulio Guagliumi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.