Ignite Creation Date:
2025-12-24 @ 4:52 PM
Ignite Modification Date:
2025-12-25 @ 2:35 PM
Study NCT ID:
NCT03825250
Status:
UNKNOWN
Last Update Posted:
2023-11-13
First Post:
2018-08-31
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
The Val-CARD Trial
Sponsor:
University of Leicester
Organization:
Study Overview
Official Title:
A Randomised Controlled Trial of Pre-surgery Sodium ValpRoate, for the Prevention of Organ Injury in Cardiac Surgery: THE Val-CARD TRIAL
Status:
UNKNOWN
Status Verified Date:
2023-11
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Val-CARD
Brief Summary:
The Val-CARD trial aims to answer the question: "Does the drug sodium valproate reduce complications affecting the heart and kidneys in patients having heart operations?" Sodium valproate is a drug commonly used in the treatment of epilepsy. Recently it has been shown to protect against heart and kidney damage in laboratory tests. This has led to trials evaluating whether it can prevent heart and kidney damage in patients. The investigators wish to evaluate whether treatment with sodium valproate for a short period can reduce levels of organ damage following heart surgery by measuring this in blood tests, exercise tests, a special x-ray measuring body fat content, a walk exercise and muscle strength tests. The investigators now want to establish if sodium valproate works by making the heart and kidney more resistant to any injury that results from the use of the heart lung machine.
Detailed Description:
This trial is a single centre, unblinded, randomised controlled trial of pre-surgery sodium valproate versus standard care (no treatment). The trial has two phases. In the first phase - the dose finding phase, 40 patients will be randomised (1:1:1:1) to three different treatment doses versus a control group of standard care (no treatment). A single sodium valproate dose will be selected based on the evaluation of compliance, toxicity and levels of Histone Deacetylase inhibition. In the second phase, the efficacy of this dose at preventing myocardial and kidney injury will then be compared to untreated controls using a 1:1 randomised parallel group design in a further 82 patients. In an optional research procedure during the efficacy phase of the trial (Phase 2) cardiometabolic status (cardiac function and visceral adiposity) will be evaluated using MRI scanning.
Patients will be screened by the investigators to assess eligibility for entry into the trial. Eligible patients undergoing cardiac surgery with CPB who consent to participate will be randomly allocated using concealed allocation as follows:
In the dose finding phase of the trial patient will be randomised in a 1:1:1:1 ratio to:
1. GROUP A: Standard care (no treatment)
2. GROUP B: Sodium valproate at a target dose of 15 mg/kg per day for 1-2 weeks pre-surgery.
3. Group C: Sodium valproate at a target dose of 15 mg/kg per day for 4-6 weeks pre-surgery.
4. Group D: Sodium valproate at a target dose of 25 mg/kg per day for 4-6 weeks pre-surgery.
In the efficacy phase of the trial patients will be randomised in a 1:1 ratio to:
1. GROUP A: Standard care (no treatment)
2. GROUP B, C or D: Sodium valproate at a target dose as determined by the dose finding phase of the trial.
The Val-CARD Trial proposes to test the overarching hypothesis that pre-surgery administration of sodium valproate will protect patients against organ damage that occurs during cardiac surgery with cardiopulmonary bypass.
The trial will test a number of specific hypotheses:
1. Pre-surgery sodium valproate will reduce the risk of post cardiac surgery organ failure.
2. Short-term (1-2 weeks) pre-surgery treatment with sodium valproate at a target dose of 15mg/kg/day will have different pharmacokinetics but comparable tolerability and protective effects on myocardial and renal signaling to long-term (4-6 weeks) treatment at a target dose of 15mg/kg/ day or 25mg/kg/day.
3. Sodium valproate will reduce the risk of post cardiac surgery myocardial injury by increasing the expression of genes that promote myocardial mitochondrial homeostasis via effects on chromatin histone deacetylation.
4. Sodium valproate will reduce the risk of post cardiac surgery acute kidney injury (AKI) by increasing the expression of genes that promote renal tubular homeostasis.
5. Sodium valproate will reduce the risk of post cardiac surgery endothelial dysfunction by increasing the expression of genes that promote endothelial homeostasis.
6. The trial interventions will be tolerated by patients and will not result in long-term adverse changes in cardiometabolic status.
Patients will be screened by the investigators to assess eligibility for entry into the trial. Eligible patients undergoing cardiac surgery with CPB who consent to participate will be randomly allocated using concealed allocation as follows:
In the dose finding phase of the trial patient will be randomised in a 1:1:1:1 ratio to:
1. GROUP A: Standard care (no treatment)
2. GROUP B: Sodium valproate at a target dose of 15 mg/kg per day for 1-2 weeks pre-surgery.
3. Group C: Sodium valproate at a target dose of 15 mg/kg per day for 4-6 weeks pre-surgery.
4. Group D: Sodium valproate at a target dose of 25 mg/kg per day for 4-6 weeks pre-surgery.
In the efficacy phase of the trial patients will be randomised in a 1:1 ratio to:
1. GROUP A: Standard care (no treatment)
2. GROUP B, C or D: Sodium valproate at a target dose as determined by the dose finding phase of the trial.
The Val-CARD Trial proposes to test the overarching hypothesis that pre-surgery administration of sodium valproate will protect patients against organ damage that occurs during cardiac surgery with cardiopulmonary bypass.
The trial will test a number of specific hypotheses:
1. Pre-surgery sodium valproate will reduce the risk of post cardiac surgery organ failure.
2. Short-term (1-2 weeks) pre-surgery treatment with sodium valproate at a target dose of 15mg/kg/day will have different pharmacokinetics but comparable tolerability and protective effects on myocardial and renal signaling to long-term (4-6 weeks) treatment at a target dose of 15mg/kg/ day or 25mg/kg/day.
3. Sodium valproate will reduce the risk of post cardiac surgery myocardial injury by increasing the expression of genes that promote myocardial mitochondrial homeostasis via effects on chromatin histone deacetylation.
4. Sodium valproate will reduce the risk of post cardiac surgery acute kidney injury (AKI) by increasing the expression of genes that promote renal tubular homeostasis.
5. Sodium valproate will reduce the risk of post cardiac surgery endothelial dysfunction by increasing the expression of genes that promote endothelial homeostasis.
6. The trial interventions will be tolerated by patients and will not result in long-term adverse changes in cardiometabolic status.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: