Treatment of Reperfusion Event by Vitamin C Infusion

Angina Pectoris Clinical Trial

— TREVI  

Official title:

Effect of Vitamin C Infusion on Coronary Reperfusion Indexes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01090895
• Other study ID #: Violi012009
• Status: Recruiting
• Phase: Phase 4
• First received: March 18, 2010
• Last updated: March 8, 2016
• Start date: March 2010
• Est. completion date: December 2018

Study information

• Verified date: March 2016
• Source: University of Roma La Sapienza
• Contact: Francesco Violi, Full Prof
• Phone: +39-06-4461933
• Email: francesco.violi[@]uniroma1.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina Pectoris

Intervention

Drug:
• Vitamin C
Intravenous infusion of vitamin C (1 g) 10 minutes before percutaneous coronary intervention.
• Placebo
Intravenous infusion of placebo(saline solution) 10 minutes before percutaneous coronary intervention.

Locations

Country	Name	City	State
Italy	Sapienza Università di Roma	Rome

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

References & Publications (8)

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. — View 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. — View Citation

Basili S, Tanzilli G, Raparelli V, Calvieri C, Pignatelli P, Carnevale R, Dominici M, Placanica A, Arrivi A, Farcomeni A, Barillà 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. — View 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. Epub 2007 Jun 13. — View 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. — View 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. Epub 2005 Mar 23. — View 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- — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Specific key observations used to measure the effect of experimental treatment in this study are the incidence of Major Adverse Cardiovascular Events.	Cardiovascular Death, Myocardial Infarction, Stent Thrombosis, Repeat Revascularization, Stroke, Transient Ischemic Attack	12 months	Yes
Secondary	Myocardial damage and microcoronary disfunction by cardiac magnetic resonance imaging	Prophylactic Vitamin C Intravenous Infusion at the time of percutaneous coronary intervention (PCI) would limit the size of damage within 7 days after PCI.	7 days	No
Secondary	Improvement of reperfusion indexes (corrected Thrombolysis In Myocardial Infarction frame count and myocardial blush grade)	Prophylactic Vitamin C Intravenous Infusion at the time of percutaneous coronary intervention (PCI) could improve the reperfusion indexes.	post PCI	No
Secondary	Early incidence of Major Adverse Cardiovascular Events.	Cardiovascular Death, Myocardial Infarction, Stent Thrombosis, Repeat Revascularization, Stroke, Transient Ischemic Attack	1 month	Yes
Secondary	Late incidence of Major Adverse Cardiovascular Events.	Cardiovascular Death, Myocardial Infarction, Stent Thrombosis, Repeat Revascularization, Stroke, Transient Ischemic Attack	3 months	Yes