A Phase 1/2 interventional study of Sodium Valproate in Cardiac Valve Disease, Coronary Artery Disease and Organ Failure, Multiple, sponsored by University of Leicester. Terminated at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-17.
Sponsored by University of Leicester · Phase 1/2, Interventional, and Treatment
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.
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:
In the efficacy phase of the trial patients will be randomised in a 1:1 ratio to:
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:
552 studies on the registry are indexed under Heart Valve Diseases; 162 are open to participants now.
This study's enrollment of 45 is below the median of 100 across 311 interventional studies indexed under Heart Valve Diseases.
Browse Heart Valve Diseases studies →University of Leicester is the lead sponsor of 170 studies on the registry; 51 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Standard of care
15 mg/kg for 1-2 weeks
Drug: Sodium Valproate
15 mg/kg for 4-6 weeks
Drug: Sodium Valproate
25 mg/kg for 4-6 weeks
Drug: Sodium Valproate
Treatment with Sodium Valproate vs. Control Discovery phase - 4 arms: 15 mg/kg for 1-2 weeks; 15mg/kg for 4-6 weeks; 25 mg/kg for 4-6 weeks; Control Efficiency phase - 2 arms: Treatment group selected from previous phase; Control
Change of Serum Creatinine level
Measurement of serum creatinine level and expressed as umol/L.
Time frame: Baseline, 2 weeks, 4 weeks, 0-6, 6-12, 24, 48, 72, and 96 hours post-operatively
Change of Serum Troponin I level
Measurement of serum Troponin level and expressed as ng/L.
Time frame: Baseline, at 0-6, 6-12, 24, 48 and 72 hours post-operatively
Change in Multiple organ dysfunction - Sepsis-related Organ Failure Assessment (SOFA) Score)
Range 0-3, 3 being the worse score
Time frame: Baseline, 4 weeks, 0-6, 24, 48, 72 and 96 hours
NGAL (Neutrophil gelatinase associated lipocalcin)
Measurement of NGAL level and expressed as μg/L.
Time frame: Baseline, day before surgery, 6-12, 24 and 48 hours post-surgery.
Lung Injury - Arterial alveolar oxygen (PaO2/FiO2) ratios
Measurement of PaO2/FiO2 ratio and expressed in kPa/L.
Time frame: Baseline, day before surgery, 24, 48, 72 and 96 hours post-surgery.
AST (Aspartate Transaminase)
Measurement of AST levels in serum and expressed in IU/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Time frame: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
ALT (Alanine Transaminase)
Measurement of ALT levels in serum and expressed in IU/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Time frame: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Bilirubin
Measurement of Bilirubin levels in serum and expressed in μmol/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Time frame: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Alkaline Phosphatase
Measurement of Alkaline Phosphatase levels in serum and expressed in IU/L. Acute liver injury will be defined as an acute derangement of three times the upper limit of normal.
Time frame: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Serum Amylase
Measurement of Amylase levels in serum and expressed in IU/L. Acute pancreatitis will be defined as a serum amylase concentration \>1000 ng/ml.
Time frame: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Assessment of resource use - Time until extubation
Time frame: Time (hours) measured from the start of surgery - to extubation (up to 30 days)
Length of stay in Intensive Care Unit
Number of hours between admission and discharge from the Intensive Care Unit (ICU).
Time frame: Time (hours) measured from the start of surgery to discharge from ICU (up to 30 days)
Length of Stay in Hospital
Number of days between the date of surgery and discharge from the hospital.
Time frame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Sepsis
Sepsis is defined as: Suspected or documented infection and an acute change in total Sepsis-related Organ Failure Assessment (SOFA) score ≥2 points consequent to the infection. Range of SOFA is 0 to 3, 3 being the worse score.
Time frame: Baseline, 4 weeks before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Rate of mortality
Rate of mortality at 30-day and 1 year from the date of surgery.
Time frame: Within 30-days from surgery and at 1 year from surgery
Bleeding and Transfusion
The total number of units of red cells and other blood components transfused during the operative period and post-operative hospital stay
Time frame: Intra-operative and between time of surgery and hospital discharge up to two weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Adverse events as assessed for type and severity by CTCAE v4.0
Time frame: Post-operative up to 3 months follow-up from time of surgery
Mechanism study: Mithocondrial function of microvessels from tissue biopsies
50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.
Time frame: At time of surgery
Mechanism study: microRNAs isolation from microvessels
The findings will be represented by the frequency (%) of identified microRNAs. 50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies.
Time frame: At time of surgery
Mechanism study: Chromatin Immunoprecipitation (ChIP) of microvessels from tissue biopsies
To identify protein binding sites that may help identify functional elements in the genome. Findings will be represented by the number (n) of binding sites. 50-100 mg biopsies obtained from pedicled left internal mammary artery biopsies.
Time frame: At time of surgery
Mechanism study: Mithocondrial function measured in right atrium myocardium tissue biopsies
50-100 mg myocardial biopsies will be obtained from the right atrium at surgery. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.
Time frame: At time of surgery
Mechanism study: microRNA isolation from right atrium myocardium tissue biopsies
50-100 mg myocardial biopsies will be obtained from the right atrium at surgery. The findings will be represented by the frequency (%) of identified microRNAs.
Time frame: At time of surgery
Mechanism study: Chromatin Immunoprecipitation (ChIP) in right atrium myocardium tissue biopsies
50-100 mg myocardial biopsies will be obtained from the right atrium at surgery. To identify protein binding sites that may help identify functional elements in the genome. Findings will be represented by the number (n) of binding sites.
Time frame: At time of surgery
Mechanism study: Mithocondrial function measured in adipose tissue biopsies
Adipose tissue collected from epicardial fat at time of surgery. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.
Time frame: At time of surgery
Mechanism study: microRNA isolation in adipose tissue biopsies
Adipose tissue collected from epicardial fat at time of surgery. The findings will be represented by the frequency (%) of identified microRNAs.
Time frame: At time of surgery
Mechanism study: Chromatin Immunoprecipitation (ChIP) in adipose tissue biopsies
Adipose tissue collected from epicardial fat at time of surgery. To identify protein binding sites that may help identify functional elements in the genome. Findings will be represented by the number (n) of binding sites.
Time frame: At time of surgery
Mechanism study: Measurement of microvesicles in urine samples
Identification of microvesicles. The findings will be represented by the frequency (%) of each identified microvesicle.
Time frame: 1 day before surgery, 12 and 24 hours following surgery
Mechanism study: Measurement of microRNAs in urine samples
The findings will be represented by the frequency (%) of identified microRNAs.
Time frame: 1 day before surgery, 12 and 24 hours following surgery
Mechanism study: Measurement of histone acetylation in urine samples
The findings will be reported as acetylated H3 (ug/mg) over time (hours)
Time frame: 1 day before surgery, 12 and 24 hours following surgery
Mechanism study: Measurement of gene expression in urine samples
Whole genome sequencing will be achieved through ATAC sequencing. The identified genes will be characterised by average expression count over ATAC.
Time frame: 1 day before surgery, 12 and 24 hours following surgery
Mechanism study: Cardiac Magnetic Resonance Imaging - Cardiac Function
Assessment of cardiac function, by assessing ventricular function. This will be expressed as ejection fraction (%). Intravenous contrast will be administered via an indwelling venous catheter.
Time frame: Baseline, 1 day before surgery and 3 months following surgery
Mechanism study: Cardiac Magnetic Resonance Imaging - Cardiac adiposity content
Assessment of cardiac adiposity content. A percentage of adipose tissue over total body mass will be calculated. Intravenous contrast will be administered via an indwelling venous catheter.
Time frame: Baseline, 1 day before surgery and 3 months following surgery
Mechanism study: Cardiac Magnetic Resonance Imaging - Visceral adiposity content
Assessment of visceral adiposity content. A percentage of adipose tissue over total body mass will be calculated. Intravenous contrast will be administered via an indwelling venous catheter.
Time frame: Baseline, 1 day before surgery and 3 months following surgery
Plan to share: No
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This study is terminated, as verified in Nov 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Valproic Acid