Albumin in Cardiac Surgery

NCT02560519 | Completed Phase 4

• 1 other identifier: EPA1
• Study Type: interventional
• Target: 1,386
• Locations: 1 country
• Sites: 1

Brief Summary

Colloid solutions are widely used for volume replacement therapy because of their high oncotic pressure, which could reduce interstitial fluid shifting. Human albumin is the only colloid solution of biologic origin with a molecular weight of 60 kDa. As the most abundant plasma protein, it has physiological importance in the well-being of the endothelial glycocalyx. Older studies in septic patients, however, did not show any benefit of albumin over saline solution. Crystalloid solutions, such as Ringer's acetate, do not impair neither renal function nor coagulation, but their volume expanding effect is questionable. For several reasons (use of heart-lung machine, systemic inflammation, coagulation disturbances), patients undergoing cardiac surgery need especially large amounts of fluids. However, there are no large trials comparing albumin solutions to crystalloid solutions cardiac surgery. This double-blinded trial will randomize according to a power analysis 1250 cardiac surgery patients (=625+625) at Meilahti hospital to use either 4% Albumin or Ringer's acetate solutions for both priming of the heart-lung machine and perioperative volume replacement therapy. The primary efficacy and safety endpoint of this study is the incidence of major adverse events (MAE), defined as a composite endpoint of all-cause mortality, acute myocardial infarction, acute heart failure or low output syndrome, resternotomy, stroke, certain arrhythmias, major bleeding, infections compromising post-procedural rehabilitation, acute kidney injury within 90 days postoperatively. The secondary outcomes are total number of MAEs, major adverse cardiac events (MACE), perioperative fluid balance, blood product transfusions, blood loss, acute kidney injury, days alive without mechanical ventilation/outside ICU/at home in 90 days as well as 90-day mortality. Blood samples for biochemical analyses will be collected at four perioperative time points. This trial will provide data about efficacy and safety of 4% albumin in cardiac surgery patients. The biochemical mechanisms of albumin will be assessed.

Conditions

C.Surgical Procedure; Cardiac

Keywords

human serum albumin solution; Cardiopulmonary Bypass

Outcome Measures

Primary Outcomes (1)

• Major adverse events

  The number of patients with at least one major adverse event during 90 days postoperatively:all-cause death;acute myocardial injury (increase in CK-MB at least 10 times as high as the upper normal limit);new onset of acute heart failure/low output syndrome requiring intravenous inotropic agents,intra-aortic balloon pump support and/or ECMO,resternotomy/subxiphoidal pericardial drainage;stroke;major arrhythmia (ventricular fibrillation off-CPB,ventricular tachycardia off-CPB,new onset atrial fibrillation of permanent nature requiring anticoagulation, permanent pacing dependency of new onset);major bleeding (chest tube blood loss at 18 hours over 20 mL/kg) or requiring 5 or more units of red blood cell transfusion or an equivalent volume of washed red blood cells within intervention time;infection compromising post-procedural rehabilitation;acute kidney injury(postoperative increase of creatinine at least 2 times compared to the preoperative level),renal replacement therapy

  90 days

Study Arms (2)

Ringers acetate solution

ACTIVE COMPARATOR

Ringer-Acetat Baxter Viaflo® (Baxter Finland, Finland): Ringer-Acetat is iso-oncotic solution.Pharmacodynamic and pharmacokinetic properties: The osmotic effect is approximately the same as that of blood plasma. Electrolytes are given to receive or to keep normal osmotic conditions in the extracellular as well as the intracellular compartment. Acetate is oxidized into bicarbonate, mainly in the muscles and peripheral tissues and gives a weak alkalizing effect. Qualitative and quantitative list of composition: 1000 ml of Ringer-Acetat Baxter Viaflo contains 5.86 g sodium chloride, 0.30 g potassium chloride dihydrate, 0.29 g, 0.20 g magnesium chloride hexahydrate, 4.08 g sodium acetate trihydrate. List of excipients: Water for injections, Hydrochloric acid.

Drug: Ringers acetate solution

Albumin solution

EXPERIMENTAL

Albuman® 200g/L (Sanquin, the Netherlands) is a solution containing 200 g/l (20%) of total protein of which at least 95% is human albumin.The solution contains 100 mmol/l of sodium (2.3 g/L). Pharmacodynamic properties: Albumin stabilises circulating blood volume and is a carrier of hormones, enzymes, medicinal products and toxins. Pharmacokinetic properties. Under normal conditions, the average half-life of albumin is about 19 days. Albuman® 40g/L is a solution containing 40 g/l (4%) of total protein of which at least 95% is human albumin. The solution contains 140 mmol/l of sodium (3.2 g/L).

Drug: Albumin solution

Interventions

Albumin solution DRUG

Albumin solution will used for priming of the CPB(cardio-pulmonary bypass) tubing. : A mixture of 20% (200 mg/mL) albumin (Albuman® 200 g/L, Sanquin, the Netherlands) with Ringer's acetate solution in the final albumin concentration of 4%. During surgery and the first 24 hours of ICU treatment, albumin 4% solution will be used up to 3200 mL for volume replacement therapy. Ringer's acetate solution is used thereafter, i.e. if more than 3200 mL are needed for volume replacement therapy.The volume replacement therapy is not determined but will be based on the clinical decision.

Also known as: Albumin

Albumin solution

Ringers acetate solution DRUG

The Ringers acetate solution will be used for priming of the CPB tubing. The CPB priming volume comprises only of Ringer´s solution. During surgery and the first 24 hours of ICU treatment,Ringer´s acetate solution will be used up to 3200 mL for volume replacement therapy. Ringer's acetate solution is used thereafter, i.e. if more than 3200 mL are needed for volume replacement therapy during the second study phase. The volume replacement therapy is not determined but will be based on the clinical decision.

Ringers acetate solution

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• following primary or repeat open heart surgery procedures, either independently or in combinations:CABG,aortic valve replacement/repair, mitral valve replacement/repair,tricuspid valve replacement/repair,the MAZE procedure or its modifications,surgery on the aortic root or ascending aorta not requiring hypothermic circulatory arrest;
• scheduled for elective surgery or operated during the index admission

You may not qualify if:

• immediate emergency surgery (i.e. no time for recruitment)
• end-stage kidney disease (estimated GFR\<20 mL/min - based on serum/ plasma creatinine)
• hemophilia A, hemophilia B
• patient denial of the use of blood products and derivatives of blood products
• ticagrelor, prasugrel, clopidogrel,apixaban or rivaroxaban treatment within 2 days preoperatively or that of dabigatran within 3 days
• correction of a congenital heart defect
• preoperative infection compromising post-procedural rehabilitation
• preoperative heart failure / low output syndrome (preoperative inotropic support, intra-aortic balloon pump, preoperative EF(ejection fraction) \< 20 %)
• preoperative dependency of mechanical ventilation, preoperative ECMO(extra-corporeal membrane oxygenation),left ventrical mechanical assistance.

Sponsors & Collaborators

• Helsinki University Central Hospital: lead

Study Sites (1)

Helsinki University Central Hospital, Meilahti Hospital

Helsinki, Uusimaa, 00029, Finland

Location

Related Publications (2)

• Pesonen E, Vlasov H, Suojaranta R, Hiippala S, Schramko A, Wilkman E, Eranen T, Arvonen K, Mazanikov M, Salminen US, Meinberg M, Vahasilta T, Petaja L, Raivio P, Juvonen T, Pettila V. Effect of 4% Albumin Solution vs Ringer Acetate on Major Adverse Events in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass: A Randomized Clinical Trial. JAMA. 2022 Jul 19;328(3):251-258. doi: 10.1001/jama.2022.10461.

  PMID: 35852528 DERIVED

• Vlasov H, Juvonen T, Hiippala S, Suojaranta R, Peltonen M, Schramko A, Arvonen K, Salminen US, Kleine Budde I, Eranen T, Mazanikov M, Meinberg M, Vahasilta T, Wilkman E, Pettila V, Pesonen E. Effect and safety of 4% albumin in the treatment of cardiac surgery patients: study protocol for the randomized, double-blind, clinical ALBICS (ALBumin In Cardiac Surgery) trial. Trials. 2020 Feb 28;21(1):235. doi: 10.1186/s13063-020-4160-3.

  PMID: 32111230 DERIVED

MeSH Terms

Interventions

Albumins

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Eero Pesonen, MD.,PhD

  Helsinki University Central Hospital

  STUDY CHAIR

• Hanna Vlasov, MD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: September 25, 2015
• Study Start: March 21, 2017
• Primary Completion: April 13, 2020
• Study Completion: November 4, 2020
• Last Updated: November 16, 2020

Record last verified: 2020-11

Locations

FI (1)