NCT02762331

Brief Summary

Coronary artery bypass grafting (CABG) is the most common procedure performed by cardiac surgeons. Post-operative atrial fibrillation (AF) is the most common adverse event following CABG, experienced in 20-50% of patients; the highest incidence of AF occurs by the third post-operative day. Reduction of AF by various drugs is moderately effective, but involves either rate control with beta blockers or rate conversion with amiodarone after the myocardial damage processes initiating AF have already occurred. Decreasing the incidence of post-operative AF, and hence the morbidity and mortality of high-risk CABG patients, could be more fruitfully approached by targeting the upstream combined processes of inflammation and coagulation activation induced by the surgical insult and associated ischemia-reperfusion (I/R). We propose that cell damage induced by oxidative stress and I/R injury could be prevented and/or inhibited by antioxidant supplementation. Specifically the investigators hypothesize that high-dose intravenous (IV) vitamin C supplementation will ameliorate ROS and therefore damp down upstream inflammatory processes, leading to a reduction of downstream adverse events with demonstrable links to inflammation processes, such as AF.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2017

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 27, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

May 4, 2016

Completed
8 months until next milestone

Study Start

First participant enrolled

January 1, 2017

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 13, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 13, 2018

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

June 24, 2019

Completed
Last Updated

June 24, 2019

Status Verified

March 1, 2019

Enrollment Period

1.2 years

First QC Date

April 27, 2016

Results QC Date

April 12, 2018

Last Update Submit

March 28, 2019

Conditions

Disorder of Vitamin CAtrial FibrillationComplications Due to Coronary Artery Bypass GraftHeart Valve Disease

Keywords

Vitamin CCoronary Artery Bypass GraftingAtrial FibrillationCardiac Valve Repair

Outcome Measures

Primary Outcomes (2)

  • Plasma Inflammatory Biomarkers

    Change in baseline inflammatory biomarkers including TNF-alpha, C-reactive protein, and interleukin-6 will be measured at 6, 24, and 48 hours following first administration of study drug.

    48 hours

  • Urinary Inflammatory Biomarker

    Change in baseline urine concentrations for neutrophil gelatinase-associated lipocalin (NGAL) will be measured at 6 and 24 hours.

    24 hours

Secondary Outcomes (4)

  • Occurence of Atrial Fibrillation

    48 hours

  • Coagulation Biomarkers

    48 hours

  • Lipidomic Biomarkers

    24 hours

  • Development of Renal Calculi

    48 hours

Study Arms (2)

Vitamin C

EXPERIMENTAL

Intravenous ascorbic acid 50 mg/kg in 50 mL normal saline every six hours for 48 hours.

Drug: Ascorbic Acid

Normal saline

PLACEBO COMPARATOR

Intravenous normal saline 50 mL every six hours for 48 hours

Drug: Placebo

Interventions

Ascorbic AcidDRUG

Comparing safety and efficacy of IV Vitamin C in CABG patients

Also known as: Vitamin C
Vitamin C
PlaceboDRUG

Placebo intervention

Also known as: Normal Saline
Normal saline

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 years
  • Scheduled for elective non-emergent valve repair or replacement, or multi-vessel CABG surgery
  • No known coagulopathy prior to surgery

You may not qualify if:

  • Emergency cardiac surgery
  • Ejection fraction \< 35%
  • Presence of autoimmune disease or currently receiving immunosuppressant therapy
  • History of renal calculi
  • Renal dysfunction (pre-operative creatinine clearance \< 40 mL/min, or serum creatinine greater than 1.8 mg/dl)
  • Known bleeding diathesis
  • Active infection, cancer or tumor
  • Prior history of atrial fibrillation
  • Single CABG procedure (one involved coronary vessel)
  • Prisoner
  • Pregnant

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Virginia Commonwealth University Health System

Richmond, Virginia, 23298, United States

Location

Related Publications (14)

  • Quality AfHRa. HCUPnet: A tool for identifying, tracking, and analyzing national hospital statistics. In: Services DoHaH, ed. Rockville, MD2014.

    BACKGROUND

  • Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012 Jan 3;125(1):188-97. doi: 10.1161/CIR.0b013e3182456d46. No abstract available.

    PMID: 22215894BACKGROUND

  • Surgeons SoT. Adult Cardiac Surgery Database: Executive Summary: 10 Years. 2012; http://www.sts.org/sites/default/files/documents/2012%20-%20AC%20-%203rdHarvestExecutiveSummary.pdf. Accessed January 14, 2014.

    BACKGROUND

  • Korantzopoulos P, Kolettis TM, Galaris D, Goudevenos JA. The role of oxidative stress in the pathogenesis and perpetuation of atrial fibrillation. Int J Cardiol. 2007 Feb 7;115(2):135-43. doi: 10.1016/j.ijcard.2006.04.026. Epub 2006 Jun 9.

    PMID: 16764958BACKGROUND

  • Rodrigo R. Prevention of postoperative atrial fibrillation: novel and safe strategy based on the modulation of the antioxidant system. Front Physiol. 2012 Apr 12;3:93. doi: 10.3389/fphys.2012.00093. eCollection 2012.

    PMID: 22518106BACKGROUND

  • Mariscalco G, Klersy C, Zanobini M, Banach M, Ferrarese S, Borsani P, Cantore C, Biglioli P, Sala A. Atrial fibrillation after isolated coronary surgery affects late survival. Circulation. 2008 Oct 14;118(16):1612-8. doi: 10.1161/CIRCULATIONAHA.108.777789. Epub 2008 Sep 29.

    PMID: 18824644BACKGROUND

  • Fukushima R, Yamazaki E. Vitamin C requirement in surgical patients. Curr Opin Clin Nutr Metab Care. 2010 Nov;13(6):669-76. doi: 10.1097/MCO.0b013e32833e05bc.

    PMID: 20689415BACKGROUND

  • Ferguson TB Jr, Coombs LP, Peterson ED; Society of Thoracic Surgeons National Adult Cardiac Surgery Database. Preoperative beta-blocker use and mortality and morbidity following CABG surgery in North America. JAMA. 2002 May 1;287(17):2221-7. doi: 10.1001/jama.287.17.2221.

    PMID: 11980522BACKGROUND

  • Halonen J, Hakala T, Auvinen T, Karjalainen J, Turpeinen A, Uusaro A, Halonen P, Hartikainen J, Hippelainen M. Intravenous administration of metoprolol is more effective than oral administration in the prevention of atrial fibrillation after cardiac surgery. Circulation. 2006 Jul 4;114(1 Suppl):I1-4. doi: 10.1161/CIRCULATIONAHA.105.000851.

    PMID: 16820555BACKGROUND

  • Wenk MR. The emerging field of lipidomics. Nat Rev Drug Discov. 2005 Jul;4(7):594-610. doi: 10.1038/nrd1776.

    PMID: 16052242BACKGROUND

  • Kunt AS, Selek S, Celik H, Demir D, Erel O, Andac MH. Decrease of total antioxidant capacity during coronary artery bypass surgery. Mt Sinai J Med. 2006 Sep;73(5):777-83.

    PMID: 17008938BACKGROUND

  • Larmann J, Theilmeier G. Inflammatory response to cardiac surgery: cardiopulmonary bypass versus non-cardiopulmonary bypass surgery. Best Pract Res Clin Anaesthesiol. 2004 Sep;18(3):425-38. doi: 10.1016/j.bpa.2003.12.004.

    PMID: 15212337BACKGROUND

  • Review Manager (RevMan) [computer program]. Version Version 5.2. Copenhagen: The Nordic Cochrane Centre; 2012.

    BACKGROUND

  • Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011 Oct 18;343:d5928. doi: 10.1136/bmj.d5928.

    PMID: 22008217BACKGROUND

MeSH Terms

Conditions

Atrial FibrillationHeart Valve Diseases

Interventions

Ascorbic AcidSaline Solution

Condition Hierarchy (Ancestors)

Arrhythmias, CardiacHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar AcidsAcids, AcyclicCarboxylic AcidsOrganic ChemicalsHydroxy AcidsCarbohydratesCrystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Results Point of Contact

Title
Donald Brophy, PharmD
Organization
Virginia Commonwealth University
dbrophy@vcu.edu
(804) 827-1455

Study Officials

  • Donald F Brophy, PharmD

    Virginia Commonwealth University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 27, 2016

First Posted

May 4, 2016

Study Start

January 1, 2017

Primary Completion

March 13, 2018

Study Completion

March 13, 2018

Last Updated

June 24, 2019

Results First Posted

June 24, 2019

Record last verified: 2019-03

Locations

US(1)