Transfusion-Associated Circulatory Overload Best Eliminated With Lasix

Sunnybrook Health Sciences Centre

Status and phase: Completed; Early Phase 1

Conditions: Transfusion-associated Circulatory Overload

Treatments: Drug: Furosemide; Drug: Normal Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT02802696

16-5032

Details and patient eligibility

About

This is a pilot double-blinded placebo-controlled randomized controlled trial (RCT) to evaluate the feasibility of conducting a multicenter, randomized, placebo-controlled trial to assess the efficacy of pre-transfusion furosemide in preventing transfusion-associated circulatory overload (TACO) in hemodynamically stable inpatients aged 65 years or older receiving a single unit red blood cell transfusion. Patients will be randomly allocated to receive either furosemide (20mg intravenous) or placebo (saline) within 60 minutes of starting a red blood cell (RBC) transfusion. Randomization will be stratified by centre and renal dysfunction (creatinine clearance ≥ 60 mL/min or < 60 mL/min). This is a blinded trial: patients, care-providers (physicians and nurses), data collectors, outcome adjudicators, and data analysts will not be aware of group allocation.

Full description

The investigators proposed this pilot study to assist us in determining the feasibility of conducting a definitive multicenter randomized trial across Canada.

Rationale:

The rationale for this study includes: (1) TACO is the leading cause of morbidity and mortality due to transfusion; (2) risk factors for TACO include older age, renal dysfunction and positive fluid balance; (3) furosemide is a diuretic commonly prescribed for fluid overload; (4) furosemide can decrease pulmonary artery pressures; and (5) clinical uncertainty as to the effect of furosemide in preventing TACO. The investigators will enroll 80 patients in this pilot study at two centers.

Hypothesis:

The investigators hypothesize that 80 patients can be enrolled in the trial within a 2-month period

Justification:

If pre-transfusion that furosemide decreases the rate of TACO with red blood cell transfusion, clinical practice worldwide would change. Over 800,000 patients in Canada receive a blood transfusion annually and many are at high risk for TACO and may benefit from this simple, low-cost intervention. This intervention could easily be generalizable worldwide. There are practical challenges related to patient recruitment, adherence to trial protocol and data collection, all of which the TACO-BEL Pilot Trial will seek to measure.

Objectives:

The primary outcome of this trial is to determine the feasibility of performing a large multi-centre, randomized, placebo-controlled trial with concealed allocation and blinded outcome assessment, adequately powered to determine a clinically significant effect of pre-transfusion furosemide on the incidence of transfusion-associated circulatory overload.

Primary outcome measure is the number of patients enrolled within a two-month period

Secondary feasibility outcome measures include:

1. Proportion of patients screened meeting eligibility criteria
2. Proportion of eligible patients consenting to participate
3. Proportion of consenting patients receiving the allocated treatment
4. Proportion of treated patients completing follow-up assessment
5. Proportion of patients in which blinding was maintained throughout study

Research Method:

Patients meeting inclusion criteria will be identified by reviewing transfusion orders received by the blood transfusion laboratory or by referral from ordering physicians; these patients will then be approached by study personnel to obtain pre-transfusion informed consent. Randomization will be performed by pharmacy at the time of drug preparation. The randomization code will be generated in random blocks of 4 to 6, stratified by center, and renal function at time of randomization (creatinine clearance < 60 and ≥ 60 mL/min) using a computer based randomization program.

Intervention:

Patients will be administered a bolus dose of 20mg furosemide (20mg/2mL) intravenously within 60 minutes prior to the start of the red blood cell transfusion. Patients randomized to placebo will be administered an equal volume of normal saline intravenously immediately within 60 minutes prior to the start of the red blood cell transfusion.

Enrollment: 80 patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 65 years.
• Receiving a single unit red blood cell transfusion

Exclusion criteria

• Active bleeding (active visible bleeding, required 2 or more RBC units in the preceding 24 hours, drop in Hb > 20 g/L in the preceding 24 hours);
• Hemodynamically unstable (systolic blood pressure < 90 mmHg or on inotropes);
• Anticipated major surgical procedure within 24 hours of enrolment;
• Presence of hyponatremia (Na < 130 mmol/L);
• Presence of hypokalemia (K < 3.5 mmol/L);
• Dialysis or creatinine clearance < 30 mL/min;
• Order for platelet or plasma transfusion at same time;
• Allergy to furosemide;
• Risk of withholding furosemide felt by attending physician to place patient at excessive risk of harm;
• Previously enrolled in the study;
• Plan for discharge on the day of randomization;
• Unable to provide informed consent.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Furosemide

Experimental group

Description:

Diuretic

Treatment:

Drug: Furosemide

Placebo

Placebo Comparator group

Description:

Normal saline

Treatment:

Drug: Normal Saline