Thiamine Supplementation in High Risk Cardiac Surgery Patients

Study Overview
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Brief Summary
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This pilot trial will evaluate the ability of thiamine to affect on postoperative vasoplegia in high risk cardiac surgery patients

Detailed Description
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Thiamine has a pivotal role and is an essential cofactor for pyruvate dehydrogenase activity. Widely known wet beri-beri is developed due to thiamine deficiency and characterized by vasodilatory shock and despaired oxygen extraction leading to kidney, heart and central nervous system dysfunction. Thiamine deficiency is often underestimated and even in primary absence of vitamin B1 deficiency, high-consumptive state of many critical illness and cardiac surgery itself can lead to its lack. Reported that in patients on chronic dialysis and patients with AKI requiring RRT thiamine deficiency is a usual finding. In cross-sectional observational study it has been shown that up to 33% of patients with a diagnosis of congestive heart failure (CHF) had thiamine deficiency due to chronic loop diuretic use. Also reported that 96% of patients (21 of 23) with heart failure receiving loop diuretic therapy (daily dose: 80-240 mg furosemide) developed thiamine deficiency. In prospective observational trial it has been shown that plasma thiamine levels were decreased after CABG surgery. In a secondary analysis of a randomized, double-blind, placebo-controlled trial conducted in septic patients, thiamine supplementation showed highly-promising renal protective effect. Need for RRT was 8 patients (21%) in placebo group and 1 patient (3%) in thiamine group (p=0.04). On the other hand it was unable to show any benefit of thiamine supplementation in patients undergoing CABG surgery. Although, postoperative oxygen consumption was significantly increased among patients receiving thiamine. Nevertheless, existing evidence suggests that thiamine supplementation might be an attractive strategy in counteracting organ dysfunction and thus morbidity and mortality in high-risk cardiac surgical patients.

Official Title
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Thiamine Supplementation in High Risk Cardiac Surgery Patients

Conditions
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Cardiac Surgery

Intervention / Treatment
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* Drug: Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline
* Drug: Normal saline (100ml)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Valve surgery + CABG that required cardiac surgery with CPB Aged 18 years or older Signed informed consent Exclusion Criteria: Emergency surgery Chronic kidney disease of G4-G5 categories according to KDIGO criteria (at least one of the following present for > 3 months: glomerular filtration rate ≤ 29 ml/min/1.73 m2, history of kidney transplantation) Known allergy to thiamine Pregnancy Current enrollment into another RCT (in the last 30 days) Previous enrollment and randomisation into the APPLY trial Administration of thiamine in the previous 30 day

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Thiamine group<br> | Drug: Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline<br>* After anesthesia induction After separation from CPB On the evening of the day of surgery (22:00) On POD 1 twice a day at 8:00 and 22:00 On POD 2 twice a day at 8:00 and 22:00 (if patient is still in ICU) On POD 3 twice a day at 8:00 and 22:00 (if patient is still in ICU)<br>|
| Placebo Comparator: Placebo group<br> | Drug: Normal saline (100ml)<br>* After anesthesia induction After separation from CPB On the evening of the day of surgery (22:00) On POD 1 twice a day at 8:00 and 22:00 On POD 2 twice a day at 8:00 and 22:00 (if patient is still in ICU) On POD 3 twice a day at 8:00 and 22:00 (if patient is still in ICU)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | Recruitment of trial patients: successful recruitment is defined as 2 patients per week on average | 8 month | 
| Compliance with the protocol | Successful compliance with protocol is defined as ≥ 90% of prescribed intervention being administered across all patients | 8 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vasoinotropic score | dosage of vasoinotropic agents and total vasopressor/norepinephrine equivalent dose | 3 days | 
| Peak lactate level after CPB weaning to 48 hours |  | 48 hours | 
| The value of postoperative peak serum creatinine concentration during 3 postoperative days |  | 3 days | 
| The incidence of acute kidney injury (AKI) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria during ICU stay |  | 30 days | 
| The daily incidence of cardiovascular and renal dysfunction according to Sequential Organ Failure Assessment (SOFA) score during 48 hours postoperatively |  | 48 hours | 
| Rates of postoperative complications |  | 30 days | 
| Incidence of Treatment-Emergent Adverse Events | The safety of high dose IV thiamine supplementation will be evaluated by comparison of adverse, serious adverse events and routinely assessed biochemical parameters (i.e. complete blood count, coagulation parameters, standard biochemistry, etc.) | 30 days | 
| Availability of data needed | We expect that loss of follow up will not exceed 5% and data loss less than 10% | 8 month | 
| 7-day all-cause mortality (or mortality at any time during the first hospitalization) |  | 7 days | 
| 30-day all-cause mortality |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thiamine, Thiamine Supplementation, Vasoplegia Syndrome, Inotropic support, Cardiac surgery, Renal Failure