Vitamin C and its effect on the kidneys after open heart surgery

ISRCTN	ISRCTN98572043
DOI	https://doi.org/10.1186/ISRCTN98572043
Secondary identifying numbers	2017-2020

Submission date: 02/07/2018
Registration date: 30/11/2018
Last edited: 08/06/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Loss of kidney function after heart surgery is a complex complication with high mortality (death rate). The aim of this study is to find out whether Vitamin C supplementation decreases the loss of kidney function after open heart surgery.

Who can participate?
Adult patients requiring open heart surgery

What does the study involve?
Participants are randomly allocated to either receive vitamin C or not (control group) before surgery, during surgery and for 5 days after surgery. Kidney function is assessed during surgery and for 5 days after surgery.

What are the possible benefits and risks of participating?
Vitamin C could be potentially a potent kidney protective agent, with practically no expected side effects or risks.

Where is the study run from?
1. University Medical Center Maribor (Slovenia)
2. Institute of Cardiovascular Diseases Vojvodina (Serbia)

When is the study starting and how long is it expected to run for?
November 2017 to September 2020

Who is funding the study?
University Medical Center Maribor (Slovenia)

Who is the main contact?
Assoc. Prof. Miha Antonic, MD, PhD

Contact information

Dr Anze Djordjevic
Public

Ljubljanska ulica 5
Maribor
2000
Slovenia

Phone	+386 (0)40 260 231
Email	anze.djordjevic@ukc-mb.si

Study information

Study design	Interventional randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Prevention
Scientific title	Effect of ascorbic acid supplementation on acute kidney injury after open heart surgery
Study objectives	1. Ascorbic acid supplementation decreases loss of kidney function in all surgeries 2. Ascorbic acid supplementation decreases loss of kidney function in urgent surgeries 3. Ascorbic acid supplementation decreases loss of kidney function in patients with decreased kidney function and are not on renal replacement therapy (RRT) 4. The main mechanism for acute kidney injuries (AKI) after cardiovascular surgeries is via reactive oxygen species (ROS) and their effect on lipid peroxidation
Ethics approval(s)	Slovenian National Ethics Committee, 22/05/2018, ref: 0120-268/2018/4
Health condition(s) or problem(s) studied	Acute kidney injury
Intervention	Patients will be randomized according to their day of birth - the ones on even days will be the control group (no supplement) and the ones on odd days will be the test group (supplement). Ascorbic acid supplementation protocol: Before surgery (best in the OR, during intubation/central venous catheter placement/arterial line placement): 2 g During surgery (best immediately before decross-clamping of aorta): 2 g Postoperative day (POD) 1: 1 g/8 h POD 2: 1 g/8 h POD 3: 1 g/8 h POD 4: 1 g/8 h POD 5: 1 g/8 h In total: 19 g The trialists will observe two levels in this study: clinical and molecular. In Maribor alone, gas chromatography and mass spectrometry will be used to determine malondyaldehide concentration in the serum of a subgroup of operated patients. Malondyaldehide has been shown as a relevant measuring tool for ROS involvement in lipid peroxidation. It is assumed that it is following a linear model: the more the malondyaldehide in serum, the more ROS in the body. Approximately 100 patient (a subgroup of all included patients) will be divided into two subgroups (depending on ascorbic acid supplementation), their serum samples will be collected intraoperatively, and once a day five days postoperatively to determine malondyaldehide concentration as a function of time. On the other hand, the trialists will examine the clinical level in all enrolled 400 patients at both institutions (Maribor and Sremska Kamenica). Through creatinine and urea levels, glomerular filtration rate and diuresis, kidney function will be assessed, starting intraoperatively and once a day five days postoperatively.
Intervention type	Supplement
Primary outcome measure	Kidney function assessed using creatinine and urea levels, glomerular filtration rate and diuresis, starting intraoperatively and once a day five days postoperatively
Secondary outcome measures	ROS involvement in lipid peroxidation, assessed using malondyaldehide concentration in serum measured using gas chromatography and mass spectrometry, starting intraoperatively and once a day five days postoperatively
Overall study start date	01/11/2017
Completion date	30/09/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	400
Total final enrolment	332
Key inclusion criteria	All adult patients requiring open heart surgical procedures, regardless of the urgency (urgent vs elective) or type of procedure (coronary revascularization, valvular surgery or aortic surgery)
Key exclusion criteria	1. Chronic kidney failure on renal replacement therapy 2. Hyperoxalouria 3. History of kidney stones
Date of first enrolment	01/12/2018
Date of final enrolment	31/05/2019

Locations

Countries of recruitment

Serbia
Slovenia

Study participating centres

University Medical Center Maribor

Ljubljanska ulica 5
Maribor
2000
Slovenia

Institute of Cardiovascular Diseases Vojvodina

Put dr. Goldmana 4
Sremska Kamenica
21204
Serbia

Sponsor information

University Medical Center Maribor
Hospital/treatment centre

Ljubljanska ulica 5
Maribor
2000
Slovenia

Phone	+386 (0)2 321 1000
Email	javnosti@ukc-mb.si
Website	https://www.ukc-mb.si/
"ROR"	https://ror.org/02rjj7s91

Funders

Funder type

University/education

University Medical Center Maribor

No information available

Results and Publications

Intention to publish date	01/12/2019
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	This study is part of a PhD thesis.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Assoc. Prof. Miha Antonic, MD, PhD (miha.antonic@guest.arnes.si). The data will become available after statistical analysis and public publishment via peer-reviewed article(s). It will be available for all types of analyses.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	sub-study results	01/12/2020	10/12/2020	Yes	No
Results article		28/05/2022	08/06/2022	Yes	No

Editorial Notes

08/06/2022: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added.
10/12/2020: Publication reference added.