Clinical trial NCT01090895: Treatment of Reperfusion Event by Vitamin C Infusion
Official title: Effect of Vitamin C Infusion on Coronary Reperfusion Indexes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Angina Pectoris
Keywords: Percutaneous Coronary Intervention
Vitamin C
Biomarkers
Magnetic Risonance
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2010-03-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Hypothesis: Prophylactic Vitamin C Intravenous Infusion at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct, assessed by measurements of cardiac biomarkers, during acute myocardial infarction.

Secondary Hypotheses: Prophylactic Vitamin C Intravenous Infusion at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct, as measured by the area of delayed hyperenhancement that was seen on cardiac magnetic resonance imaging (MRI), assessed on day 5 after infarction, during acute myocardial infarction.

Detailed description: This is a multicenter, prospective, controlled, randomized study that will be conducted at up to 5 centers in Italy. All patients who meet the eligibility criteria will be randomized to receive during surgical procedure an intravenous infusion of Vitamin C or Placebo.

Patients will have repeat clinical follow-up to 5 days, 3 and 6 months and 1 year.

The new angiography evaluation will be done if necessary. The study population will consist of at least 100 patients who presented within 12 hours after the onset of chest pain, who had ST-segment elevation of more than 0.1 mV in two contiguous leads, and for whom the clinical decision was made to treat with percutaneous coronary intervention (PCI). Following confirmation of eligibility criteria, patients will be randomized in a 1:1 ratio to receive prophylactic infusion of Vitamin C or Placebo. The coronary angiograms will be assessed at a core laboratory with Quantitative Coronary Angiography.

The incidence of clinical events, including death, myocardial infarction, target vessel revascularization, stent thrombosis, will be evaluated at 1, 3, 6 and, 12 months.

Eligibility criteria: Inclusion Criteria:

* Subjects who presented within 12 hours after the onset of chest pain, who had ST-segment elevation of more than 0.1 mV in two contiguous leads, and for whom the clinical decision was made to treat with percutaneous coronary intervention (PCI)
* Patients will be eligible for the study whether they were undergoing primary PCI.
* Signed written informed consent

Exclusion Criteria:

* Patients with cardiac arrest, ventricular fibrillation, cardiogenic shock, stent thrombosis, previous acute myocardial infarction, or angina within 48 hours before infarction were not included in the study
* Patients with evidence of coronary collaterals (2-3 Rentrop) to the region at risk on initial coronary angiography (at the time of admission) will be excluded
* The patient has impaired renal function (creatinine \> 3.0 mg/dl)
* The patient has known allergies to aspirin, clopidogrel bisulfate and ticlopidine, heparin, contrast media or stainless steel that cannot be managed medically
* The patient needs therapy with warfarin
* The patient has a life expectancy less than 12 months
* Recipient of heart transplant
* The patient is currently participating in an investigational drug or another device study

Primary outcomes:
measure: Specific key observations used to measure the effect of experimental treatment in this study are the incidence of Major Adverse Cardiovascular Events.
timeFrame: 12 months
Secondary outcomes:
measure: Myocardial damage and microcoronary disfunction by cardiac magnetic resonance imaging
timeFrame: 7 days
measure: Improvement of reperfusion indexes (corrected Thrombolysis In Myocardial Infarction frame count and myocardial blush grade)
timeFrame: post PCI
measure: Early incidence of Major Adverse Cardiovascular Events.
timeFrame: 1 month
measure: Late incidence of Major Adverse Cardiovascular Events.
timeFrame: 3 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Sapienza Università di Roma
Study officials:
affiliation: Divisione di Prima Clinica Medica - Sapienza University of Rome
name: Francesco Violi, Full Prof
role: STUDY_CHAIR
References:
citation: Pignatelli P, Sanguigni V, Paola SG, Lo Coco E, Lenti L, Violi F. Vitamin C inhibits platelet expression of CD40 ligand. Free Radic Biol Med. 2005 Jun 15;38(12):1662-6. doi: 10.1016/j.freeradbiomed.2005.02.032. Epub 2005 Mar 23.
citation: Cordova C, Musca A, Violi F, Perrone A, Alessandri C. Influence of ascorbic acid on platelet aggregation in vitro and in vivo. Atherosclerosis. 1982 Jan;41(1):15-9. doi: 10.1016/0021-9150(82)90064-8.
citation: Basili S, Tanzilli G, Mangieri E, Raparelli V, Di Santo S, Pignatelli P, Violi F. Intravenous ascorbic acid infusion improves myocardial perfusion grade during elective percutaneous coronary intervention: relationship with oxidative stress markers. JACC Cardiovasc Interv. 2010 Feb;3(2):221-9. doi: 10.1016/j.jcin.2009.10.025.
citation: Violi F, Cangemi R. Antioxidant supplements and cardiovascular disease in men. JAMA. 2009 Apr 1;301(13):1335; author reply 1336-7. doi: 10.1001/jama.2009.314. No abstract available.
citation: Cangemi R, Angelico F, Loffredo L, Del Ben M, Pignatelli P, Martini A, Violi F. Oxidative stress-mediated arterial dysfunction in patients with metabolic syndrome: Effect of ascorbic acid. Free Radic Biol Med. 2007 Sep 1;43(5):853-9. doi: 10.1016/j.freeradbiomed.2007.06.002. Epub 2007 Jun 13.
citation: Basili S, Pignatelli P, Tanzilli G, Mangieri E, Carnevale R, Nocella C, Di Santo S, Pastori D, Ferroni P, Violi F. Anoxia-reoxygenation enhances platelet thromboxane A2 production via reactive oxygen species-generated NOX2: effect in patients undergoing elective percutaneous coronary intervention. Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1766-71. doi: 10.1161/ATVBAHA.111.227959. Epub 2011 Jun 2.
citation: Basili S, Tanzilli G, Raparelli V, Calvieri C, Pignatelli P, Carnevale R, Dominici M, Placanica A, Arrivi A, Farcomeni A, Barilla F, Mangieri E, Violi F. Aspirin reload before elective percutaneous coronary intervention: impact on serum thromboxane b2 and myocardial reperfusion indexes. Circ Cardiovasc Interv. 2014 Aug;7(4):577-84. doi: 10.1161/CIRCINTERVENTIONS.113.001197. Epub 2014 Jul 29.
citation: Pignatelli P, Tanzilli G, Carnevale R, Di Santo S, Loffredo L, Celestini A, Proietti M, Tovaglia P, Mangieri E, Basili S, Violi F. Ascorbic acid infusion blunts CD40L upregulation in patients undergoing coronary stent. Cardiovasc Ther. 2011 Dec;29(6):385-94. doi: 10.1111/j.1755-5922.2010.00168.x. Epub 2010 Jul 12.