Treatment of Reperfusion Event by Vitamin C Infusion - Full Text View

Purpose

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.

Condition	Intervention	Phase
Angina Pectoris	Drug: Vitamin C Drug: Placebo	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Effect of Vitamin C Infusion on Coronary Reperfusion Indexes

Resource links provided by NLM:

MedlinePlus related topics: Vitamin C

Drug Information available for: Ascorbic acid Sodium ascorbate Magnesium ascorbate

U.S. FDA Resources

Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:

Specific key observations used to measure the effect of experimental treatment in this study are the incidence of Major Adverse Cardiovascular Events. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Cardiovascular Death, Myocardial Infarction, Stent Thrombosis, Repeat Revascularization, Stroke, Transient Ischemic Attack

Secondary Outcome Measures:

Myocardial damage and microcoronary disfunction by cardiac magnetic resonance imaging [ Time Frame: 7 days ] [ Designated as safety issue: No ]
Prophylactic Vitamin C Intravenous Infusion at the time of percutaneous coronary intervention (PCI) would limit the size of damage within 7 days after PCI.
Improvement of reperfusion indexes (corrected Thrombolysis In Myocardial Infarction frame count and myocardial blush grade) [ Time Frame: post PCI ] [ Designated as safety issue: No ]
Prophylactic Vitamin C Intravenous Infusion at the time of percutaneous coronary intervention (PCI) could improve the reperfusion indexes.
Early incidence of Major Adverse Cardiovascular Events. [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
Cardiovascular Death, Myocardial Infarction, Stent Thrombosis, Repeat Revascularization, Stroke, Transient Ischemic Attack
Late incidence of Major Adverse Cardiovascular Events. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Cardiovascular Death, Myocardial Infarction, Stent Thrombosis, Repeat Revascularization, Stroke, Transient Ischemic Attack


Estimated Enrollment:	80
Study Start Date:	March 2010
Estimated Study Completion Date:	December 2018
Estimated Primary Completion Date:	October 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Vitamin C Vitamin C infusion	Drug: Vitamin C Intravenous infusion of vitamin C (1 g) 10 minutes before percutaneous coronary intervention. Other Name: Ascorbic Acid
Placebo Comparator: Placebo Saline solution	Drug: Placebo Intravenous infusion of placebo(saline solution) 10 minutes before percutaneous coronary intervention. Other Name: Saline solution

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


Ages Eligible for Study:	18 Years to 85 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01090895

Contacts


Contact: Francesco Violi, Full Prof	+39-06-4461933	francesco.violi@uniroma1.it
Contact: Stefania Basili, Ass Prof	+39-06-49974678	stefania.basili@uniroma1.it

Locations


Italy
Sapienza Università di Roma	Recruiting
Rome, Italy, 00161
Contact: Francesco Violi, Full Prof +39-06-4461933 francesco.violi@uniroma1.it
Contact: Stefania Basili, Ass Prof +39-06-49974678 stefania.basili@uniroma1.it
Sub-Investigator: Tanzilli Gaetano, Prof.
Sub-Investigator: Mangieri Enrico, Prof.
Principal Investigator: Raparelli Valeria, Prof.

Sponsors and Collaborators

University of Roma La Sapienza

Investigators


Study Chair:	Francesco Violi, Full Prof	Divisione di Prima Clinica Medica - Sapienza University of Rome

More Information

Publications:

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.

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.

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.

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.

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.

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.

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.

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.


Responsible Party:	Francesco Violi, Full professor of internal medicine, University of Roma La Sapienza
ClinicalTrials.gov Identifier:	NCT01090895 History of Changes
Other Study ID Numbers:	Violi012009
Study First Received:	March 18, 2010
Last Updated:	March 8, 2016
Health Authority:	Italy: Ethics Committee
Individual Participant Data
Plan to Share IPD:	No

Keywords provided by University of Roma La Sapienza:


Percutaneous Coronary Intervention Vitamin C Biomarkers Magnetic Risonance

Additional relevant MeSH terms:


Angina Pectoris Chest Pain Pain Neurologic Manifestations Nervous System Diseases Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases	Signs and Symptoms Vitamins Ascorbic Acid Micronutrients Growth Substances Physiological Effects of Drugs Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents

ClinicalTrials.gov processed this record on September 30, 2016

Treatment of Reperfusion Event by Vitamin C Infusion (TREVI)