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Completed

NCT Number: NCT03306732

Thiamine Supplementation in High Risk Cardiac Surgery Patients

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

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Meshalkin Research Institute of Pathology of Circulation

Novosibirsk, Russia

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

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)

Normal saline (100ml)

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)

Primary outcomes

  1. Recruitment rate

    Time frame: 8 month

    Recruitment of trial patients: successful recruitment is defined as 2 patients per week on average

  2. Compliance with the protocol

    Time frame: 8 month

    Successful compliance with protocol is defined as ≥ 90% of prescribed intervention being administered across all patients

Secondary outcomes

  1. Vasoinotropic score

    Time frame: 3 days

    dosage of vasoinotropic agents and total vasopressor/norepinephrine equivalent dose

  2. Peak lactate level after CPB weaning to 48 hours

    Time frame: 48 hours

  3. The value of postoperative peak serum creatinine concentration during 3 postoperative days

    Time frame: 3 days

  4. The incidence of acute kidney injury (AKI) according to "Kidney Disease: Improving Global Outcomes (KDIGO) criteria" during ICU stay

    Time frame: 30 days

  5. The daily incidence of cardiovascular and renal dysfunction according to Sequential Organ Failure Assessment (SOFA) score during 48 hours postoperatively

    Time frame: 48 hours

  6. Rates of postoperative complications

    Time frame: 30 days

  7. Incidence of Treatment-Emergent Adverse Events

    Time frame: 30 days

    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.)

  8. Availability of data needed

    Time frame: 8 month

    We expect that loss of follow up will not exceed 5% and data loss less than 10%

  9. 7-day all-cause mortality (or mortality at any time during the first hospitalization)

    Time frame: 7 days

  10. 30-day all-cause mortality

    Time frame: 30 days

Sponsors and collaborators

Lead sponsor

Meshalkin Research Institute of Pathology of Circulation

Network

Registry information

Acronym: APPLY

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Oct 11, 2017
Registry last updated
Jun 27, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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