Cardiac Valve DiseasePhase 1/2Val-CARDNCT03825250
The Val-CARD Trial
A Phase 1/2 study testing Sodium Valproate in people with Cardiac Valve Disease and Coronary Artery Disease, run by University of Leicester at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Valve Disease, Coronary Artery Disease, Organ Failure, Multiple
- What is being tested?
- Sodium Valproate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 6 Nov 2018to 3 Nov 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult cardiac surgery patients (≥18 years) undergoing cardiac surgery (CABG, Valve, or CABG and Valve) with cardiopulmonary bypass (CPB).
- Able, in the opinion of the investigator, and willing to give informed consent.
Who cannot join
- Emergency or salvage procedure
- Patients with end stage renal failure defined as an estimated Glomerular Filtration rate (eGFR) <15 mL/min/1.72 m2 calculated from the Modification of Diet in Renal Disease equation,1 or patients who are on long-term haemodialysis or have undergone renal transplantation.
- Patients with persistent or chronic atrial fibrillation.
- Patients with acute liver disease.
- Personal or family history of severe hepatic dysfunction, especially drug related.
- Patients allergic to sodium valproate.
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- Patients with thrombocytopaenia (platelet count <150x109 per mL).
- Patients taking long-term Histone Deacetylase Inhibitors such as sodium valproate.
- Patients taking any of the following medications: antipsychotics, MAO inhibitors, antidepressants and benzodiazepines, Lithium, Olanzepine, Phenobarbital, Primidone, Phenytoin, Carbamazepine, Lamotrigine, Felbamate.
- Patients diagnosed with a mitochondrial deficiency disorder.
- Patients with porphyria.
- Patients with known urea cycle disorders.
- Women of child bearing potential (WOCBP) are excluded from the study. A woman is defined as being of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal, unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
- Patients who are participating in another interventional clinical trial.
- Unable, in the opinion of the investigator, or unwilling to give informed consent protocol.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Glenfield Hospital
Leicester, Leicestershire, LE3 9QP
About this study
Official title: A Randomised Controlled Trial of Pre-surgery Sodium ValpRoate, for the Prevention of Organ Injury in Cardiac Surgery: THE Val-CARD TRIAL
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.
Read the 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:
- GROUP A: Standard care (no treatment)
- GROUP B: Sodium valproate at a target dose of 15 mg/kg per day for 1-2 weeks pre-surgery.
- Group C: Sodium valproate at a target dose of 15 mg/kg per day for 4-6 weeks pre-surgery.
- 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:
- GROUP A: Standard care (no treatment)
- 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:
- Pre-surgery sodium valproate will reduce the risk of post cardiac surgery organ failure.
- 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.
- 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.
- 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.
- Sodium valproate will reduce the risk of post cardiac surgery endothelial dysfunction by increasing the expression of genes that promote endothelial homeostasis.
- The trial interventions will be tolerated by patients and will not result in long-term adverse changes in cardiometabolic status.
- Being tested
- Sodium Valproate
- Keywords
- Sodium Valproate, Cardiac Surgery, Organ Injury Prevention
- Medical subject headings
- Heart Valve Diseases, Coronary Artery Disease, Multiple Organ Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium ValproateDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Group A: Control | No intervention | Standard of care |
| Group B: Sodium Valproate Treatment | Experimental | 15 mg/kg for 1-2 weeks Receives: Drug: Sodium Valproate |
| Group C: Sodium Valproate Treatment | Experimental | 15 mg/kg for 4-6 weeks Receives: Drug: Sodium Valproate |
| Group D: Sodium Valproate Treatment | Experimental | 25 mg/kg for 4-6 weeks Receives: Drug: Sodium Valproate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of Serum Creatinine level
Measurement of serum creatinine level and expressed as umol/L.
Measured: 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.
Measured: Baseline, at 0-6, 6-12, 24, 48 and 72 hours post-operatively
Secondary outcomes (31)
Change in Multiple organ dysfunction - Sepsis-related Organ Failure Assessment (SOFA) Score)
Range 0-3, 3 being the worse score
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Assessment of resource use - Time until extubation
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, 1 day before surgery and 3 months following surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2019
- Study start6 Nov 2018
- Primary completion3 Nov 2023
- Study completion3 Nov 2023
Why it stopped: Phase 1 completed recruitment and follow-up. Due to necessary suspensions for the COVID-19 pandemic, there was insufficient time remaining to complete Phase 2.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac Valve DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Unblinded two phased randomised controlled trial * Discovery phase: 4 groups (1 control, 3 treatment) * Efficiency phase: 2 groups (1 control, 1 treatment)
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gavin Murphy, MD, Study chair, BHF Professor of Cardiac Surgery, University of LeicesterMarius Roman, MD, Principal investigator, Academic Clinical Lecturer in Cardiac Surgery, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03825250
- Sponsor's protocol ID
- 0667
- Other IDs
- 2018-002076-41, 246126, 18/EM/0188, 2018
- Acronym
- Val-CARD
- Status last verified
- Nov 2023
- First submitted
- 31 Aug 2018
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial of Pre-surgery Sodium ValpRoate, for the Prevention of Organ Injury in Cardiac Surgery: THE Val-CARD TRIAL
- ClinicalTrials.gov ID
- NCT03825250
- Acronym / sponsor ID
- Val-CARD / 0667
- Keywords
- Sodium Valproate, Cardiac Surgery, Organ Injury Prevention
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Phase 1 completed recruitment and follow-up. Due to necessary suspensions for the COVID-19 pandemic, there was insufficient time remaining to complete Phase 2.
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Study start
- 6 Nov 2018 (actual)
- Primary completion
- 3 Nov 2023 (actual)
- Study completion
- 3 Nov 2023 (actual)
- First posted
- 31 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- GROUP A: Standard care (no treatment)
- GROUP B: Sodium valproate at a target dose of 15 mg/kg per day for 1-2 weeks pre-surgery.
- Group C: Sodium valproate at a target dose of 15 mg/kg per day for 4-6 weeks pre-surgery.
- 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:
- GROUP A: Standard care (no treatment)
- 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:
- Pre-surgery sodium valproate will reduce the risk of post cardiac surgery organ failure.
- 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.
- 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.
- 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.
- Sodium valproate will reduce the risk of post cardiac surgery endothelial dysfunction by increasing the expression of genes that promote endothelial homeostasis.
- The trial interventions will be tolerated by patients and will not result in long-term adverse changes in cardiometabolic status.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Unblinded two phased randomised controlled trial * Discovery phase: 4 groups (1 control, 3 treatment) * Efficiency phase: 2 groups (1 control, 1 treatment)
| Arm | Type | Receives |
|---|---|---|
| Group A: Control | No intervention | –Standard of care |
| Group B: Sodium Valproate Treatment | Experimental | Drug: Sodium Valproate15 mg/kg for 1-2 weeks |
| Group C: Sodium Valproate Treatment | Experimental | Drug: Sodium Valproate15 mg/kg for 4-6 weeks |
| Group D: Sodium Valproate Treatment | Experimental | Drug: Sodium Valproate25 mg/kg for 4-6 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult cardiac surgery patients (≥18 years) undergoing cardiac surgery (CABG, Valve, or CABG and Valve) with cardiopulmonary bypass (CPB).
- Able, in the opinion of the investigator, and willing to give informed consent.
Key exclusion criteria (15 listed)
- Emergency or salvage procedure
- Patients with end stage renal failure defined as an estimated Glomerular Filtration rate (eGFR) <15 mL/min/1.72 m2 calculated from the Modification of Diet in Renal Disease equation,1 or patients who are on long-term haemodialysis or have undergone renal transplantation.
- Patients with persistent or chronic atrial fibrillation.
- Patients with acute liver disease.
- Personal or family history of severe hepatic dysfunction, especially drug related.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium ValproateTreatment 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 | Drug | Group B: Sodium Valproate Treatment, Group C: Sodium Valproate Treatment, Group D: Sodium Valproate Treatment |
Primary outcome
Change of Serum Creatinine level
Time frame: Baseline, 2 weeks, 4 weeks, 0-6, 6-12, 24, 48, 72, and 96 hours post-operatively
Measurement of serum creatinine level and expressed as umol/L.
Change of Serum Troponin I level
Time frame: Baseline, at 0-6, 6-12, 24, 48 and 72 hours post-operatively
Measurement of serum Troponin level and expressed as ng/L.
31 secondary outcomes
Change in Multiple organ dysfunction - Sepsis-related Organ Failure Assessment (SOFA) Score)
Time frame: Baseline, 4 weeks, 0-6, 24, 48, 72 and 96 hours
NGAL (Neutrophil gelatinase associated lipocalcin)
Time frame: Baseline, day before surgery, 6-12, 24 and 48 hours post-surgery.
Lung Injury - Arterial alveolar oxygen (PaO2/FiO2) ratios
Time frame: Baseline, day before surgery, 24, 48, 72 and 96 hours post-surgery.
AST (Aspartate Transaminase)
Time frame: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
ALT (Alanine Transaminase)
Time frame: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Bilirubin
Time frame: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Alkaline Phosphatase
Time frame: Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Serum Amylase
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
Time frame: Time (hours) measured from the start of surgery to discharge from ICU (up to 30 days)
Length of Stay in Hospital
Time frame: Time (days) measured from the start of surgery to discharge from hospital (up to 90 days)
Sepsis
Time frame: Baseline, 4 weeks before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery
Rate of mortality
Time frame: Within 30-days from surgery and at 1 year from surgery
Bleeding and Transfusion
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
Time frame: Post-operative up to 3 months follow-up from time of surgery
Mechanism study: Mithocondrial function of microvessels from tissue biopsies
Time frame: At time of surgery
Mechanism study: microRNAs isolation from microvessels
Time frame: At time of surgery
Mechanism study: Chromatin Immunoprecipitation (ChIP) of microvessels from tissue biopsies
Time frame: At time of surgery
Mechanism study: Mithocondrial function measured in right atrium myocardium tissue biopsies
Time frame: At time of surgery
Mechanism study: microRNA isolation from right atrium myocardium tissue biopsies
Time frame: At time of surgery
Mechanism study: Chromatin Immunoprecipitation (ChIP) in right atrium myocardium tissue biopsies
Time frame: At time of surgery
Mechanism study: Mithocondrial function measured in adipose tissue biopsies
Time frame: At time of surgery
Mechanism study: microRNA isolation in adipose tissue biopsies
Time frame: At time of surgery
Mechanism study: Chromatin Immunoprecipitation (ChIP) in adipose tissue biopsies
Time frame: At time of surgery
Mechanism study: Measurement of microvesicles in urine samples
Time frame: 1 day before surgery, 12 and 24 hours following surgery
Mechanism study: Measurement of microRNAs in urine samples
Time frame: 1 day before surgery, 12 and 24 hours following surgery
Mechanism study: Measurement of histone acetylation in urine samples
Time frame: 1 day before surgery, 12 and 24 hours following surgery
Mechanism study: Measurement of gene expression in urine samples
Time frame: 1 day before surgery, 12 and 24 hours following surgery
Mechanism study: Cardiac Magnetic Resonance Imaging - Cardiac Function
Time frame: Baseline, 1 day before surgery and 3 months following surgery
Mechanism study: Cardiac Magnetic Resonance Imaging - Cardiac adiposity content
Time frame: Baseline, 1 day before surgery and 3 months following surgery
Mechanism study: Cardiac Magnetic Resonance Imaging - Visceral adiposity content
Time frame: Baseline, 1 day before surgery and 3 months following surgery
Results and safety
The study was stopped early (reason given: Phase 1 completed recruitment and follow-up. Due to necessary suspensions for the COVID-19 pandemic, there was insufficient time remaining to complete Phase 2.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
- Individual participant dataSharing planned: No
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Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gavin Murphy, MD study chair
BHF Professor of Cardiac Surgery, University of Leicester
Marius Roman, MD principal investigator
Academic Clinical Lecturer in Cardiac Surgery, University of Leicester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sodium Valproate in people with Cardiac Valve Disease and Coronary Artery Disease, run by University of Leicester at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Phase 1 completed recruitment and follow-up. Due to necessary suspensions for the COVID-19 pandemic, there was insufficient time remaining to complete Phase 2.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Serum Creatinine level (time frame: Baseline, 2 weeks, 4 weeks, 0-6, 6-12, 24, 48, 72, and 96 hours post-operatively). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.