Thiamine Supplementation in High Risk Cardiac Surgery Patients

NCT ID: NCT03306732

Last Updated: 2018-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-19
• Study Completion Date: 2018-06-18

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.

Conditions

Cardiac Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Thiamine group

Group Type: ACTIVE_COMPARATOR

Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline

Intervention Type: DRUG

• 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)

Placebo group

Group Type: PLACEBO_COMPARATOR

Normal saline (100ml)

Intervention Type: DRUG

• 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)

Interventions

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)

Intervention Type: DRUG

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)

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Meshalkin Research Institute of Pathology of Circulation

NETWORK

Sponsor Role: lead

Responsible Party

Efremov Sergey

MD PHD Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Meshalkin Research Institute of Pathology of Circulation

Novosibirsk, , Russia

Countries

Russia

References

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.

Reference Type: BACKGROUND

PMID: 21378251 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1867241 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20005469 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26456273 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

10

Identifier Type: -

Identifier Source: org_study_id