The Thiamine Administration After Cardiac Surgery Trial

NCT04641104 | Completed Phase 4

• 1 other identifier: TAACS trial
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Thiamine (Vitamin B1) is essential for cell function and as a co-factor of the enzyme Pyruvate Dehydrogenase to initiate the Krebs cycle and thus the aerobic metabolism of glucose. We hypothesize that thiamine supplementation improves the clearance of lactate in the first 24 hours after cardiac surgery with extracorporeal circulation in patients with high lactate concentration.

Conditions

Lactate Blood Increase; Thiamine Deficiency

Outcome Measures

Primary Outcomes (1)

• Lactate

  Lactate level will be specifically be measured 24h post-ICU admission to evaluate the effect of thiamine versus placebo.

  24 hours

Secondary Outcomes (5)

• Fluid balance

  48 hours

• Inotropes

  48 hours

• Mechanical ventilation

  48 hours

• Length of ICU stay

  5 days

• Length of hospital stay

  30 days

Study Arms (2)

Thiamine

EXPERIMENTAL

Patients in this arm will receive a solution of 500 mg of Thiamine Hydrocloride in a solution of 100 ml of NaCl 0.9%.

Drug: Thiamine 500 MG

Placebo

PLACEBO COMPARATOR

Patients in this arm will receive a solution of 100 ml of NaCl 0.9% alone.

Drug: Placebo

Interventions

Thiamine 500 MG DRUG

A solution of 500 mg of Thiamine Hydrocloride in a solution of 100 ml of NaCl 0.9% will be administered post-cardiac surgery in patients with lactate levels ≥ 2 mmol / L in the first 6 hours post-ICU admission.

Also known as: Thiamine

Thiamine

Placebo DRUG

100 ml of NaCl 0.9% will be administered in the placebo group.

Placebo

Eligibility Criteria

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

You may qualify if:

• Adult patients scheduled for elective cardiac surgery with extra-corporeal circulation in the CHU de Charleroi between November 2020 and December 2021. Written informed consent will be obtained from each patient/ family member participating in the study.

You may not qualify if:

• Patients already supplemented with vitamins
• Patients with an allergy to thiamine
• Patients who are priorly treated with linezolide, antiretrovirals and/or metformin treatment within 48 hours preoperatively
• Patients with mitochondrial disorders
• Patients with Child Pugh C cirrhosis
• Patients with a history of epilepsy with tonic-clonic movements postoperatively.
• Pregnant patients

Sponsors & Collaborators

• Sarah Saxena: lead
• CHU de Charleroi: collaborator

Study Sites (1)

CHU-Charleroi Hopital Civil Marie Curie

Charleroi, Hainaut, Belgium

Location

Related Publications (16)

• Frank RA, Leeper FJ, Luisi BF. Structure, mechanism and catalytic duality of thiamine-dependent enzymes. Cell Mol Life Sci. 2007 Apr;64(7-8):892-905. doi: 10.1007/s00018-007-6423-5.

  PMID: 17429582 RESULT

• Collie JTB, Greaves RF, Jones OAH, Lam Q, Eastwood GM, Bellomo R. Vitamin B1 in critically ill patients: needs and challenges. Clin Chem Lab Med. 2017 Oct 26;55(11):1652-1668. doi: 10.1515/cclm-2017-0054.

  PMID: 28432843 RESULT

• Flannery AH, Adkins DA, Cook AM. Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU. Crit Care Med. 2016 Aug;44(8):1545-52. doi: 10.1097/CCM.0000000000001659.

  PMID: 27002274 RESULT

• Nichol AD, Egi M, Pettila V, Bellomo R, French C, Hart G, Davies A, Stachowski E, Reade MC, Bailey M, Cooper DJ. Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study. Crit Care. 2010;14(1):R25. doi: 10.1186/cc8888. Epub 2010 Feb 24.

  PMID: 20181242 RESULT

• Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV, Bellamy SL, Christie JD. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med. 2009 May;37(5):1670-7. doi: 10.1097/CCM.0b013e31819fcf68.

  PMID: 19325467 RESULT

• Sterling SA, Puskarich MA, Shapiro NI, Trzeciak S, Kline JA, Summers RL, Jones AE; Emergency Medicine Shock Research Network (EMSHOCKNET). Characteristics and outcomes of patients with vasoplegic versus tissue dysoxic septic shock. Shock. 2013 Jul;40(1):11-4. doi: 10.1097/SHK.0b013e318298836d.

  PMID: 23649098 RESULT

• Casserly B, Phillips GS, Schorr C, Dellinger RP, Townsend SR, Osborn TM, Reinhart K, Selvakumar N, Levy MM. Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med. 2015 Mar;43(3):567-73. doi: 10.1097/CCM.0000000000000742.

  PMID: 25479113 RESULT

• Vellinga NAR, Boerma EC, Koopmans M, Donati A, Dubin A, Shapiro NI, Pearse RM, van der Voort PHJ, Dondorp AM, Bafi T, Fries M, Akarsu-Ayazoglu T, Pranskunas A, Hollenberg S, Balestra G, van Iterson M, Sadaka F, Minto G, Aypar U, Hurtado FJ, Martinelli G, Payen D, van Haren F, Holley A, Gomez H, Mehta RL, Rodriguez AH, Ruiz C, Canales HS, Duranteau J, Spronk PE, Jhanji S, Hubble S, Chierego M, Jung C, Martin D, Sorbara C, Bakker J, Ince C; microSOAP study group. Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis. Crit Care. 2017 Oct 18;21(1):255. doi: 10.1186/s13054-017-1842-7.

  PMID: 29047411 RESULT

• Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, Tomlanovich MC. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004 Aug;32(8):1637-42. doi: 10.1097/01.ccm.0000132904.35713.a7.

  PMID: 15286537 RESULT

• Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. doi: 10.1001/jama.2010.158.

  PMID: 20179283 RESULT

• Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, Willemsen SP, Bakker J; LACTATE study group. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010 Sep 15;182(6):752-61. doi: 10.1164/rccm.200912-1918OC. Epub 2010 May 12.

  PMID: 20463176 RESULT

• Pan J, Peng M, Liao C, Hu X, Wang A, Li X. Relative efficacy and safety of early lactate clearance-guided therapy resuscitation in patients with sepsis: A meta-analysis. Medicine (Baltimore). 2019 Feb;98(8):e14453. doi: 10.1097/MD.0000000000014453.

  PMID: 30813144 RESULT

• Donnino MW, Miller J, Goyal N, Loomba M, Sankey SS, Dolcourt B, Sherwin R, Otero R, Wira C. Effective lactate clearance is associated with improved outcome in post-cardiac arrest patients. Resuscitation. 2007 Nov;75(2):229-34. doi: 10.1016/j.resuscitation.2007.03.021. Epub 2007 Jun 20.

  PMID: 17583412 RESULT

• Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T, Wolfe R, Moskowitz A, Smithline H, Ngo L, Cocchi MN; Center for Resuscitation Science Research Group. Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study. Crit Care Med. 2016 Feb;44(2):360-7. doi: 10.1097/CCM.0000000000001572.

  PMID: 26771781 RESULT

• Costa NA, Gut AL, de Souza Dorna M, Pimentel JA, Cozzolino SM, Azevedo PS, Fernandes AA, Zornoff LA, de Paiva SA, Minicucci MF. Serum thiamine concentration and oxidative stress as predictors of mortality in patients with septic shock. J Crit Care. 2014 Apr;29(2):249-52. doi: 10.1016/j.jcrc.2013.12.004. Epub 2013 Dec 14.

  PMID: 24412011 RESULT

• Donnino MW, Carney E, Cocchi MN, Barbash I, Chase M, Joyce N, Chou PP, Ngo L. Thiamine deficiency in critically ill patients with sepsis. J Crit Care. 2010 Dec;25(4):576-81. doi: 10.1016/j.jcrc.2010.03.003. Epub 2010 Jun 19.

  PMID: 20646908 RESULT

MeSH Terms

Conditions

Hyperlactatemia; Thiamine Deficiency

Interventions

Thiamine

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• MIchael Piagnerelli, MD; PHD

  CHU de Charleroi, Belgium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Model Details: This is a monocentric randomized, controlled, double blind study in patients undergoing elective cardiac surgery with extra corporal circulation. Anesthesia management of these patients is standardised in terms of volume-controlled ventilation, fluid and inotropes management. Randomization of 100 patients for the administration, of a solution of 500 mg of Thiamine Hydrocloride in a solution of 100 ml of NaCl 0.9% versus a solution of 100 ml of NaCl 0.9% alone in adult patients (≥ 18 years-old) with a lactate ≥ 2 mmol / L in the first 6 hours of ICU admission.

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 23, 2020
• Study Start: November 20, 2020
• Primary Completion: October 3, 2022
• Study Completion: October 3, 2022
• Last Updated: November 17, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)