Vitamin C in Cardiac Surgery Patients

June 15, 2021 updated by: Deepak Singh, Geisinger Clinic

Advancing the Cardiovascular Science of Vitamin C in Cardiac Surgery Patients

Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery that increases the incidence of stroke, kidney injury and death. Vitamin C has been shown to decrease the incidence of POAF follow cardiac surgery, but the optimal dose has not been identified. With this project, the investigators plan to gather pharmacokinetic and dose-response data for vitamin C in the cardiac surgery population. The investigators plan to conduct a small interventional pilot study investigating the pharmacokinetics and pharmacodynamics of Vitamin C in patients undergoing coronary artery bypass graft (CABG) surgery. Patients enrolled will receive an intravenous dose of Vitamin C the day before surgery and the day after. Patients will have blood samples obtained with each dose for analysis of vitamin C concentrations and several biomarkers of oxidative stress. Analysis of samples will be performed within the Department of Pharmaceutical Sciences at Wilkes University.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The pathophysiology of post-operative atrial fibrillation (POAF) in cardiac surgery patients has not been fully elucidated, but inflammation and oxidative stress are associated with its occurrence. Increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and production of glutathione and nitrotyrosine have been found to occur in animal models of atrial fibrillation and patients who develop POAF. Similarly, malondialdehyde (MDA), a biomarker of lipid peroxidation, has also been shown to increase during cardiac surgery, and be significantly more elevated in patients who develop POAF. Cardiac surgery patients supplemented with ascorbic acid have reduced expression of NADPH oxidase and levels of MDA, glutathione and nitrotyrosine, and reduced POAF rates. Ascorbic acid supplementation has demonstrated a significant reduction in POAF in small clinical trials enrolling patients undergoing cardiac surgery. Collectively, these findings show that ascorbic acid prevents POAF in a novel way compared to recommended therapies such as beta-blockers and amiodarone, without the risk of significant side effects. However, the doses of ascorbic acid utilized in clinical trials have been found to inadequately suppress the production of inflammatory markers associated with POAF. Therefore, the maximum effect of ascorbic acid for POAF prevention may not have been realized in clinical trials published to date. These suboptimal responses may be attributable to known variances in medication pharmacokinetics in the cardiac surgery population that lead to reduced medication bioavailability, metabolism and elimination. The variation in ascorbic acid pharmacokinetics in this population is unknown. Thus, the contribution of the proposed research is expected to be determination of the pharmacokinetic profile of ascorbic acid and its concentration-response relationship with oxidative biomarkers associated with POAF in the cardiac surgery population.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Wyoming Valley Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 79 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients 21 to 79 years of age admitted to Geisinger Wyoming Valley (GWV) and scheduled to undergo urgent CABG
  • Planned utilization of cardiopulmonary bypass during the surgical procedure

Exclusion Criteria:

  • Body mass index greater than 30 kg/m2
  • Estimated creatinine clearance less than 30 ml/min
  • History of persistent or permanent atrial fibrillation
  • Condition associated with oxidative stress or inflammation (e.g. chronic rheumatic, inflammatory or neoplastic disease, recent infection, etc.)
  • Currently taking corticosteroids, non-steroidal anti-inflammatory drugs or deferoxamine
  • History of oxalate kidney stones
  • Currently pregnant
  • History of allergic reaction to ascorbic acid products
  • Currently taking any herbals or supplements (not including a multivitamin or calcium)
  • Enrolled in another research study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ascorbic Acid
4 patients will receive 15 mg/kg of ascorbic acid IV the day before and after CABG surgery; 4 patients will receive 30 mg/kg of ascorbic acid IV the day before and after CABG surgery. The maximum dose of ascorbic acid will be 2 g.
Drug: Ascorbic Acid
Ascorbic acid doses will be mixed in 100 mL normal saline and infused over 60 minutes. The postoperative dose will be given on postoperative day #1.
Other Names:
  • Vitamin C

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ascorbate maximum serum concentration (Cmax)
Time Frame: 1 year
Maximum serum concentration of ascorbate obtained after drug administration.
1 year
Half-life of serum ascorbate (T1/2)
Time Frame: 1 year
The amount of time is takes for the serum concentration of ascorbate to decrease by half.
1 year
Elimination rate constant of ascorbate (Ke)
Time Frame: 1 year
The rate at which ascorbate is eliminated from the body
1 year
Area under the concentration-time curve for serum ascorbate (AUC)
Time Frame: 1 year
Describes the overall concentration in the body given an administered dose of ascorbic acid.
1 year
Change in biomarker concentrations
Time Frame: Change within 24 hours; preoperative compared to postoperative
This will consist of the concentrations of NADP+, NADPH, MDA, GGS and nitrotyrosine in blood and atrial tissue samples.
Change within 24 hours; preoperative compared to postoperative

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Geisinger Clinic

Collaborators

Wilkes University

Investigators

  • Principal Investigator: Deepak Singh, MD, Geisinger Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 6, 2017

Primary Completion (ACTUAL)

May 31, 2019

Study Completion (ACTUAL)

May 31, 2019

Study Registration Dates

First Submitted

April 5, 2017

First Submitted That Met QC Criteria

April 19, 2017

First Posted (ACTUAL)

April 21, 2017

Study Record Updates

Last Update Posted (ACTUAL)

June 16, 2021

Last Update Submitted That Met QC Criteria

June 15, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-0463 (Other Identifier: M D Anderson Cancer Center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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