Clinical trial NCT03306732: Thiamine Supplementation in High Risk Cardiac Surgery Patients
Official title: Thiamine Supplementation in High Risk Cardiac Surgery Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiac Surgery
Keywords: Thiamine
Thiamine Supplementation
Vasoplegia Syndrome
Inotropic support
Cardiac surgery
Renal Failure
Lead sponsor: Meshalkin Research Institute of Pathology of Circulation
Sponsor class: NETWORK
First posted: 2017-10-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Recruitment rate
timeFrame: 8 month
measure: Compliance with the protocol
timeFrame: 8 month
Secondary outcomes:
measure: Vasoinotropic score
timeFrame: 3 days
measure: Peak lactate level after CPB weaning to 48 hours
timeFrame: 48 hours
measure: The value of postoperative peak serum creatinine concentration during 3 postoperative days
timeFrame: 3 days
measure: The incidence of acute kidney injury (AKI) according to "Kidney Disease: Improving Global Outcomes (KDIGO) criteria" during ICU stay
timeFrame: 30 days
measure: The daily incidence of cardiovascular and renal dysfunction according to Sequential Organ Failure Assessment (SOFA) score during 48 hours postoperatively
timeFrame: 48 hours
measure: Rates of postoperative complications
timeFrame: 30 days
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 30 days
measure: Availability of data needed
timeFrame: 8 month
measure: 7-day all-cause mortality (or mortality at any time during the first hospitalization)
timeFrame: 7 days
measure: 30-day all-cause mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: Novosibirsk
country: Russian Federation
facility: Meshalkin Research Institute of Pathology of Circulation
Study officials:
References:
citation: Wiesen P, Van Overmeire L, Delanaye P, Dubois B, Preiser JC. Nutrition disorders during acute renal failure and renal replacement therapy. JPEN J Parenter Enteral Nutr. 2011 Mar;35(2):217-22. doi: 10.1177/0148607110377205.
citation: Seligmann H, Halkin H, Rauchfleisch S, Kaufmann N, Motro M, Vered Z, Ezra D. Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study. Am J Med. 1991 Aug;91(2):151-5. doi: 10.1016/0002-9343(91)90007-k.
citation: Donnino MW, Cocchi MN, Smithline H, Carney E, Chou PP, Salciccioli J. Coronary artery bypass graft surgery depletes plasma thiamine levels. Nutrition. 2010 Jan;26(1):133-6. doi: 10.1016/j.nut.2009.06.004.
citation: Andersen LW, Holmberg MJ, Doherty M, Khabbaz K, Lerner A, Berg KM, Donnino MW. Postoperative Lactate Levels and Hospital Length of Stay After Cardiac Surgery. J Cardiothorac Vasc Anesth. 2015 Dec;29(6):1454-60. doi: 10.1053/j.jvca.2015.06.007. Epub 2015 Jun 6.