Cardiac SurgeryPhase 4APPLYNCT03306732
Thiamine Supplementation in High Risk Cardiac Surgery Patients
A Phase 4 study testing Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline and Normal saline (100ml) in people with Cardiac Surgery, run by Meshalkin Research Institute of Pathology of Circulation at 1 site in Russia.
Trial summary
This pilot trial will evaluate the ability of thiamine to affect on postoperative vasoplegia in high risk cardiac surgery patients Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Surgery
- What is being tested?
- Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline and Normal saline (100ml)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteRussia
- Study dates
- 19 Oct 2017to 18 Jun 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Valve surgery + CABG that required cardiac surgery with CPB
- Aged 18 years or older
- Signed informed consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Russia1 site
Meshalkin Research Institute of Pathology of Circulation
Novosibirsk
About this study
This pilot trial will evaluate the ability of thiamine to affect on postoperative vasoplegia in high risk cardiac surgery patients
Read the 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
- Being tested
- Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline, Normal saline (100ml)
- Keywords
- Thiamine, Thiamine Supplementation, Vasoplegia Syndrome, Inotropic support, Cardiac surgery, Renal Failure
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thiamine hydrochloride (200mg) dissolved in 100 ml of normal salineDrug
- 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)
| Study group | Role | What they receive |
|---|---|---|
| Thiamine group | Active comparator | Not described Receives: Drug: Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline |
| Placebo group | Placebo comparator | Not described Receives: Drug: Normal saline (100ml) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment rate
Recruitment of trial patients: successful recruitment is defined as 2 patients per week on average
Measured: 8 month
Compliance with the protocol
Successful compliance with protocol is defined as ≥ 90% of prescribed intervention being administered across all patients
Measured: 8 month
Secondary outcomes (10)
Vasoinotropic score
dosage of vasoinotropic agents and total vasopressor/norepinephrine equivalent dose
Measured: 3 days
Peak lactate level after CPB weaning to 48 hours
Measured: 48 hours
The value of postoperative peak serum creatinine concentration during 3 postoperative days
Measured: 3 days
The incidence of acute kidney injury (AKI) according to "Kidney Disease: Improving Global Outcomes (KDIGO) criteria" during ICU stay
Measured: 30 days
The daily incidence of cardiovascular and renal dysfunction according to Sequential Organ Failure Assessment (SOFA) score during 48 hours postoperatively
Measured: 48 hours
Rates of postoperative complications
Measured: 30 days
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.)
Measured: 30 days
Availability of data needed
We expect that loss of follow up will not exceed 5% and data loss less than 10%
Measured: 8 month
7-day all-cause mortality (or mortality at any time during the first hospitalization)
Measured: 7 days
30-day all-cause mortality
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2017
- Study start19 Oct 2017
- Primary completion18 May 2018
- Study completion18 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiac SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Meshalkin Research Institute of Pathology of Circulation
- Sponsor type
- Research network
- Responsible party
- Principal investigator, Efremov Sergey, Meshalkin Research Institute of Pathology of Circulation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03306732
- Sponsor's protocol ID
- 10
- Acronym
- APPLY
- Status last verified
- Jun 2018
- First submitted
- 19 Sep 2017
- Last updated
- 27 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 21378251Seligmann 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.
PubMed 1867241Donnino 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.
PubMed 20005469Andersen 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.
PubMed 26456273
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thiamine Supplementation in High Risk Cardiac Surgery Patients
- ClinicalTrials.gov ID
- NCT03306732
- Acronym / sponsor ID
- APPLY / 10
- Conditions
- Cardiac Surgery
- Keywords
- Thiamine, Thiamine Supplementation, Vasoplegia Syndrome, Inotropic support, Cardiac surgery, Renal Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Meshalkin Research Institute of Pathology of CirculationResearch network
- Study start
- 19 Oct 2017 (actual)
- Primary completion
- 18 May 2018 (actual)
- Study completion
- 18 Jun 2018 (actual)
- First posted
- 11 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thiamine group | Active comparator | Drug: Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline |
| Placebo group | Placebo comparator | Drug: Normal saline (100ml) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Valve surgery + CABG that required cardiac surgery with CPB
- Aged 18 years or older
- Signed informed consent
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) | Drug | Thiamine group |
| 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) | Drug | Placebo group |
Primary outcome
Recruitment rate
Time frame: 8 month
Recruitment of trial patients: successful recruitment is defined as 2 patients per week on average
Compliance with the protocol
Time frame: 8 month
Successful compliance with protocol is defined as ≥ 90% of prescribed intervention being administered across all patients
10 secondary outcomes
Vasoinotropic score
Time frame: 3 days
Peak lactate level after CPB weaning to 48 hours
Time frame: 48 hours
The value of postoperative peak serum creatinine concentration during 3 postoperative days
Time frame: 3 days
The incidence of acute kidney injury (AKI) according to "Kidney Disease: Improving Global Outcomes (KDIGO) criteria" during ICU stay
Time frame: 30 days
The daily incidence of cardiovascular and renal dysfunction according to Sequential Organ Failure Assessment (SOFA) score during 48 hours postoperatively
Time frame: 48 hours
Rates of postoperative complications
Time frame: 30 days
Incidence of Treatment-Emergent Adverse Events
Time frame: 30 days
Availability of data needed
Time frame: 8 month
7-day all-cause mortality (or mortality at any time during the first hospitalization)
Time frame: 7 days
30-day all-cause mortality
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2018.
- Background: PubMed 21378251Wiesen 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.
- Background: PubMed 1867241Seligmann 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.
- Background: PubMed 20005469Donnino 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.
- Background: PubMed 26456273Andersen 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.
Related trials for Cardiac Surgery
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
Not yet recruitingObservational study
Systematic Intraoperative Cell Salvage in On-Pump Cardiac Surgery Within a Mature Patient Blood Management Programme
Cardiac Surgical Procedures, Blood Transfusion
Recruiting
Change in Platelet Lipid Metabolism and Procoagulant Phenotype Induced by Cardiopulmonary Bypass. Impact on Postoperative Inflammatory Response and Bleeding Complications During Cardiac Surgery.
Cardiac Surgery, Cardiopulmonary Bypass
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Thiamine hydrochloride (200mg) dissolved in 100 ml of normal saline and Normal saline (100ml) in people with Cardiac Surgery, run by Meshalkin Research Institute of Pathology of Circulation at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment rate (time frame: 8 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03306732, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2018; AzTrials last refreshed its copy on 6 Nov 2026.