The Val-CARD Trial

NCT03825250 | Unknown Phase 1 DMC

• 4 other identifiers: 06672018-002076-4124612618/EM/0188
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiac Valve Disease; Coronary Artery Disease; Organ Failure, Multiple

Keywords

Sodium Valproate; Cardiac Surgery; Organ Injury Prevention

Outcome Measures

Primary Outcomes (2)

• Change of Serum Creatinine level

  Measurement of serum creatinine level and expressed as umol/L.

  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.

  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)

  Baseline, 4 weeks, 0-6, 24, 48, 72 and 96 hours

• NGAL (Neutrophil gelatinase associated lipocalcin)

  Baseline, day before surgery, 6-12, 24 and 48 hours post-surgery.

• Lung Injury - Arterial alveolar oxygen (PaO2/FiO2) ratios

  Baseline, day before surgery, 24, 48, 72 and 96 hours post-surgery.

• AST (Aspartate Transaminase)

  Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery

• ALT (Alanine Transaminase)

  Baseline, day before surgery, 0-6, 6-12, 24, 48, 72 and 96 hours post-surgery

Study Arms (4)

Group A: Control

NO INTERVENTION

Standard of care

Group B: Sodium Valproate Treatment

EXPERIMENTAL

15 mg/kg for 1-2 weeks

Drug: Sodium Valproate

Group C: Sodium Valproate Treatment

EXPERIMENTAL

15 mg/kg for 4-6 weeks

Drug: Sodium Valproate

Group D: Sodium Valproate Treatment

EXPERIMENTAL

25 mg/kg for 4-6 weeks

Drug: Sodium Valproate

Interventions

Sodium Valproate DRUG

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

Group B: Sodium Valproate Treatment; Group C: Sodium Valproate Treatment; Group D: Sodium Valproate Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (1)

Glenfield Hospital

Leicester, Leicestershire, LE3 9QP, United Kingdom

RECRUITING

MeSH Terms

Conditions

Heart Valve Diseases; Coronary Artery Disease; Multiple Organ Failure

Interventions

Valproic Acid

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Shock; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Gavin Murphy, MD

  BHF Professor of Cardiac Surgery, University of Leicester

  STUDY CHAIR

• Marius Roman, MD

  Academic Clinical Lecturer in Cardiac Surgery, University of Leicester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marius Roman, MD

CONTACT

+44(0)1162525841; mariusroman@nhs.net

Hardeep Aujla

CONTACT

0116250; ha200@le.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Unblinded two phased randomised controlled trial * Discovery phase: 4 groups (1 control, 3 treatment) * Efficiency phase: 2 groups (1 control, 1 treatment)

Study Record Dates

• First Submitted: August 31, 2018
• First Posted: January 31, 2019
• Study Start: November 6, 2018
• Primary Completion: October 7, 2024
• Study Completion: October 7, 2024
• Last Updated: November 13, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)