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Transfusion-Associated Circulatory Overload Best Eliminated With Lasix

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ClinicalTrials.gov Identifier: NCT02802696
Recruitment Status : Completed
First Posted : June 16, 2016
Last Update Posted : June 26, 2017
Sponsor:
Collaborators:
University Health Network, Toronto
Canadian Blood Services
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Tracking Information
First Submitted Date  ICMJE February 29, 2016
First Posted Date  ICMJE June 16, 2016
Last Update Posted Date June 26, 2017
Study Start Date  ICMJE June 2016
Actual Primary Completion Date March 17, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2016)
Number of patients enrolled [ Time Frame: 2 months period ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02802696 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2016)
  • Proportion of patients screened meeting eligibility criteria [ Time Frame: 2 months ]
  • Proportion of eligible patients consenting to participate [ Time Frame: 2 months ]
  • Proportion of patient receiving the allocated treatment [ Time Frame: 2 months ]
  • Proportion of treated patients completing follow-up assessment [ Time Frame: 2 months ]
  • Proportion of patient in which blinding was maintained throughout study [ Time Frame: 2 months ]
  • Vital Signs [ Time Frame: Baseline and 6 hours post transfusion ]
    Change in vital signs immediately post-transfusion and at 6 hours post-transfusion
  • Positive end-expiratory pressure [ Time Frame: Baseline and 6 hours post transfusion ]
    For patients on mechanical ventilation pre-transfusion, change in positive end-expiratory pressure
  • Inspiratory oxygen [ Time Frame: Baseline and 6 hours post transfusion ]
    change in fraction of inspiratory oxygen at 6 hours post-transfusion
  • Incidence of TACO within 6 hours from completion of transfusion [ Time Frame: within 6 hours ]
  • Severity of TACO-graded as per the Public Health Agency of Canada's Transfusion Transmitted Injuries Surveillance System [ Time Frame: within 6 hours ]
  • Validation of TACO as per criteria adopted from the US Center for Disease Control [ Time Frame: within 6 hours ]
  • Change in plasma brain natriuretic peptide(BNP) [ Time Frame: Baseline and Day 1 ]
  • Net fluid balance at 24 hours from start of transfusion- all intravenously-administered fluids (including the transfused blood product and the study intervention) [ Time Frame: Within 24 hours ]
  • Proportion of patients developing hyponatremia or hypokalemia by Day 1 [ Time Frame: By Day 1 ]
  • Proportion of patients developing hypotension [ Time Frame: Within 24 hours ]
  • Proportion of patients developing acute kidney injury [ Time Frame: Within 24 hours ]
  • Need for increased supplemental oxygen is defined as any increase in oxygen flow ≥ 1 L/hr or (fraction of inspired oxygen)FiO2 ≥ 5% of 1 hour duration or longer, prompted by either patient symptoms or a fall in oxygen saturation(SpO2) ≥ 5% [ Time Frame: Within 24 hours ]
  • Need for inotropic support is defined as the initiation of a continuous infusion of dopamine, dobutamine, epinephrine, or norepinephrine [ Time Frame: Within 24 hours ]
  • Need for additional diuretic or vasodilatory therapy is defined by the prescription of non-study furosemide, hydrochlorothiazide, metolazone, or either transdermal or intravenous nitroglycerin [ Time Frame: Within 24 hours ]
  • Occurrence of acute coronary syndrome or new arrhythmia [ Time Frame: within 7 days ]
  • Mortality during hospital stay [ Time Frame: Upto 30 days ]
  • Length of hospital stay [ Time Frame: From date of admission until the date discharge from an acute care hospital or date of death from any cause, whichever came first, assessed up to 30 days. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Transfusion-Associated Circulatory Overload Best Eliminated With Lasix
Official Title  ICMJE Pre-transfusion Furosemide in Patients at High Risk of Transfusion-associated Circulatory Overload - The Transfusion-Associated Circulatory Overload Best Eliminated With Lasix (TACO-BEL) Study: A Pilot Randomized Controlled Trial
Brief Summary 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Transfusion-associated Circulatory Overload
Intervention  ICMJE
  • Drug: Furosemide
    A bolus dose of 20mg furosemide (20mg/2mL) will be given intravenously by slow intravenous push within 60 minutes prior to the start of the red blood cell transfusion; infusion via minibag is also acceptable.
    Other Name: Lasix
  • Drug: Normal Saline
    A single bolus dose of 2 mL normal saline will be given intravenously immediately within 60 minutes prior to the start of the red blood cell transfusion; infusion via minibag is also acceptable.
    Other Name: 0.9% Sodium Chloride
Study Arms  ICMJE
  • Experimental: Furosemide
    Diuretic
    Intervention: Drug: Furosemide
  • Placebo Comparator: Placebo
    Normal saline
    Intervention: Drug: Normal Saline
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 13, 2016)
80
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 15, 2017
Actual Primary Completion Date March 17, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02802696
Other Study ID Numbers  ICMJE 16-5032
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Sunnybrook Health Sciences Centre
Study Sponsor  ICMJE Sunnybrook Health Sciences Centre
Collaborators  ICMJE
  • University Health Network, Toronto
  • Canadian Blood Services
Investigators  ICMJE
Principal Investigator: Jeannie Callum, MD Sunny Brook Health Sciences Centre
PRS Account Sunnybrook Health Sciences Centre
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP