Thiamine Supplementation in High Risk Cardiac Surgery Patients

Cardiac Surgery Clinical Trial

— APPLY  

Official title:

Thiamine Supplementation in High Risk Cardiac Surgery Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03306732
• Other study ID #: 10
• Status: Completed
• Phase: Phase 4
• Start date: October 19, 2017
• Est. completion date: June 18, 2018

Study information

• Verified date: June 2018
• Source: Meshalkin Research Institute of Pathology of Circulation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 18, 2018
• Est. primary completion date: May 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Surgery

Intervention

Drug:
• Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline
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)
• Normal saline (100ml)
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)

Locations

Country	Name	City	State
Russian Federation	Meshalkin Research Institute of Pathology of Circulation	Novosibirsk

Sponsors (1)

Lead Sponsor	Collaborator
Meshalkin Research Institute of Pathology of Circulation

Country where clinical trial is conducted

Russian Federation, 

References & Publications (4)

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. — View 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. Erratum in: Nutrition. 2011 Sep;27(9):982. Salciccoli, Justin [corrected to Salciccioli, Justin]. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment rate	Recruitment of trial patients: successful recruitment is defined as 2 patients per week on average	8 month
Primary	Compliance with the protocol	Successful compliance with protocol is defined as = 90% of prescribed intervention being administered across all patients	8 month
Secondary	Vasoinotropic score	dosage of vasoinotropic agents and total vasopressor/norepinephrine equivalent dose	3 days
Secondary	Peak lactate level after CPB weaning to 48 hours		48 hours
Secondary	The value of postoperative peak serum creatinine concentration during 3 postoperative days		3 days
Secondary	The incidence of acute kidney injury (AKI) according to "Kidney Disease: Improving Global Outcomes (KDIGO) criteria" during ICU stay		30 days
Secondary	The daily incidence of cardiovascular and renal dysfunction according to Sequential Organ Failure Assessment (SOFA) score during 48 hours postoperatively		48 hours
Secondary	Rates of postoperative complications		30 days
Secondary	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
Secondary	Availability of data needed	We expect that loss of follow up will not exceed 5% and data loss less than 10%	8 month
Secondary	7-day all-cause mortality (or mortality at any time during the first hospitalization)		7 days
Secondary	30-day all-cause mortality		30 days