TACO Crossover TRIAL

• ClinicalTrials.gov Identifier: NCT03135457
• Recruitment Status: Completed
• First Posted: May 1, 2017
• Last Update Posted: August 4, 2020
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Information provided by (Responsible Party): A.P.J. Vlaar, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Description

Brief Summary:

This is an open-label, prospective crossover randomized controlled trial to investigate wether TACO is solely hydrostatic pressure overload or arises from a combination of hydrostatic pressure overload and capillary leakage, by investigating the difference in change in static pressure parameters (PCWP), dynamic volume parameters (PICCO) as indirect measurements of volume status and capillary leakage after autologous transfusion or saline infusion. The investigators will estimate effective circulating volume following autologous transfusion or saline infusion. Furthermore, the investigators will investigate the effect of fluid loading on the microcirculation.

Condition or disease	Intervention/treatment	Phase
Transfusion-associated Circulatory Overload; Blood Transfusion Reaction	Procedure: Autologous RBC transfusion; Procedure: Saline transfusion	Not Applicable

Detailed Description:

Coronary arterial bypass grafting surgery patients with reduced left ventricular function will be allocated to either infusion of 300mL saline with a subsequent autologous RBC (cell saver) transfusion of 300 mL at a rate of 10mL/min, or the same in the reversed order. Prior to start of the intervention, 15 minutes following start of infusion and a the end of infusion, the investigators will measure right-ventricular pressure and wedge pressure (PCWP), as well as extravascular lung water index (EVLWI) and CO estimation through PICCO® and Pulmonary Artery Catheter. The investigators will identify fluid responsiveness by performing a passive leg raise test (PLR). The investigators aim to measure total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI), and blood vessel diameters (Øbv) from the oral microcirculation by CytoCam microscope system. The investigators will estimate the effective circulating blood and plasma volume through dilutional infusion of indocyanine green prior to initial infusion, between and at the end of subsequent infusion.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Open-label, prospective cross-over randomized controlled trial.
• Masking: Double (Participant, Care Provider)
• Masking Description: Masking of investigator is not possible due to nature of intervention.
• Primary Purpose: Basic Science
• Official Title: A Cross-over Randomized Controlled Trial; Pulmonary Edema Detection After Fluid Loading With Blood Versus Saline in Patients After CABG
• Actual Study Start Date: August 16, 2017
• Actual Primary Completion Date: March 13, 2020
• Actual Study Completion Date: April 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Group A; Patients will receive infusion of 300mL saline with a subsequent autologous Red Blood Cells (RBC) transfusion of 300 mL at a rate of 10mL/min	Procedure: Autologous RBC transfusion; Autologous RBC transfusion 300ml 10 ml/min; Procedure: Saline transfusion; Saline transfusion 300ml 10ml/min
Group B; Patients will receive infusion of 300mL autologous RBC with a subsequent saline transfusion of 300 mL at a rate of 10mL/min	Procedure: Autologous RBC transfusion; Autologous RBC transfusion 300ml 10 ml/min; Procedure: Saline transfusion; Saline transfusion 300ml 10ml/min

Outcome Measures

Primary Outcome Measures :

1. Hydrostatic pressure overload [ Time Frame: 1 hour ]
   Hydrostatic pressure overload defined as delta pulmonary capillary wedge pressure

Secondary Outcome Measures :

1. Capillary leakage [ Time Frame: 1 hour ]
   Capillary leakage defined as delta extra vascular lung water index
2. Cardiac output [ Time Frame: 1 hour ]
   Volume overload measured by cardiac output
3. Mean arterial pressure [ Time Frame: 1 hour ]
   Volume overload measured by mean arterial pressure
4. Pulse pressure variation [ Time Frame: 1 hour ]
   Volume overload measured by pulse pressure variation
5. Stroke volume variation [ Time Frame: 1 hour ]
   Volume overload measured by stroke volume variation
6. Extra vascular lung water index [ Time Frame: 1 hour ]
   Volume overload measured by extra vascular lung water index
7. Systemic vascular resistance [ Time Frame: 1 hour ]
   Volume overload measured by systemic vascular resistance
8. Colloid osmotic pressure [ Time Frame: 1 hour ]
   Colloid osmotic pressure measured by membrane colloid osmometer
9. Estimated circulating volume [ Time Frame: 1 hour ]
   Estimated circulating blood volume measured by indocyanine green
10. Estimated circulating volume [ Time Frame: 1 hour ]
    Estimated circulating plasma volume measured by indocyanine green
11. Microcirculation [ Time Frame: 1 hour ]
    Total vessel density in the sublingual microcirculation measured by Cytocam
12. Microcirculation [ Time Frame: 1 hour ]
    Perfused vessel density in the sublingual microcirculation measured by Cytocam
13. Microcirculation [ Time Frame: 1 hour ]
    Proportion of perfused vessels in the sublingual microcirculation measured by Cytocam
14. Microcirculation [ Time Frame: 1 hour ]
    Microvascular flow index in the sublingual microcirculation measured by Cytocam
15. Microcirculation [ Time Frame: 1 hour ]
    Blood vessel diameters in the sublingual microcirculation measured by Cytocam
16. Fluid responsiveness [ Time Frame: 1 hour ]
    Fluid responsiveness defined by Passive Leg Raise test (increase in cardiac output > 10%)
17. TACO [ Time Frame: 6 hours ]
    Transfusion associated circulatory overload criteria 6 hours after infusion of autologous blood transfusion

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age >18 years
2. Elective (non-redo) coronary arterial bypass grafting surgery
3. Reduced left ventricular ejection fraction (<55%)
4. Transfusion of autologous blood (cell saver blood, 300ml, HCT60%, 30min)
5. Informed consent

Exclusion Criteria:

1. Patients with no indication for autologous RBC transfusion
2. Patients with pulmonary hypertension, congenital heart disease, mitral or tricuspid valve disease.
3. Contraindications for PAC placement; coagulopathy, bundle branch block, defibrillator or pacemaker (risk of displacement). External pacemaker placed during surgery is no exclusion criterium.
4. Patients for acute, non-elective surgery
5. Chronic kidney disease stage 4 or higher (eGFR < 30)
6. Massive transfusion
7. Previous randomization in the current trial
8. Postoperative ongoing bleeding
9. Bypass duration > 2 hours
10. Infusion of high dose corticosteroids
11. Hemodynamic instability with a mean arterial pressure (MAP) < 60 mmHg, central venous pressure > 20 mmHg or dependence on high dosages of inotropic drugs after admittance to the ICU
12. Severe arrhythmias
13. Development of severe pulmonary edema during infusion of autologous blood or saline.
14. Elevated liver enzymes
15. Iodine allergy

Contacts and Locations

Locations

Netherlands

Academisch Medisch Centrum - Universiteit van Amsterdam

Amsterdam, Netherlands

Sponsors and Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

• Principal Investigator: Alexander Vlaar, MD PhD MBA; Academisch Medisch Centrum - Universiteit van Amsterdam

More Information

Publications:

Delaney M, Wendel S, Bercovitz RS, Cid J, Cohn C, Dunbar NM, Apelseth TO, Popovsky M, Stanworth SJ, Tinmouth A, Van De Watering L, Waters JH, Yazer M, Ziman A; Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Transfusion reactions: prevention, diagnosis, and treatment. Lancet. 2016 Dec 3;388(10061):2825-2836. doi: 10.1016/S0140-6736(15)01313-6. Epub 2016 Apr 12.

• Responsible Party: A.P.J. Vlaar, MD PhD MBA, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• ClinicalTrials.gov Identifier: NCT03135457
• Other Study ID Numbers: NL59191.018.16
• First Posted: May 1, 2017
• Last Update Posted: August 4, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Transfusion Reaction; Hematologic Diseases; Immune System Diseases