Transfusion-associated Circulatory OverloadEarly Phase 1NCT02802696
Transfusion-Associated Circulatory Overload Best Eliminated With Lasix
A Early Phase 1 study testing Furosemide and Normal Saline in people with Transfusion-associated Circulatory Overload, run by Sunnybrook Health Sciences Centre at 3 sites in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Transfusion-associated Circulatory Overload
- What is being tested?
- Furosemide and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 3 sitesCanada
- Study dates
- Jun 2016to 15 Apr 2017
- Phase
- Early Phase 1
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Age ≥ 65 years.
- Receiving a single unit red blood cell transfusion
Who cannot join
- 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;
Show all 12Show fewer
- 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 locations and contacts
3 sites in 1 country.
Canada3 sites
Canadian Blood Services
Toronto, Ontario, K1G 4J5
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
University Health Network
Toronto, Ontario, M5G 2C4
About this study
Official title: 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
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.
Read the 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:
- Proportion of patients screened meeting eligibility criteria
- Proportion of eligible patients consenting to participate
- Proportion of consenting patients receiving the allocated treatment
- Proportion of treated patients completing follow-up assessment
- 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.
- Being tested
- Furosemide, Normal Saline
- Keywords
- Transfusion, Transfusion Medicine, Diuretic
- Medical subject headings
- Transfusion Reaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FurosemideDrug
Also called Lasix
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.
Normal SalineDrug
Also called 0.9% Sodium Chloride
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.
| Study group | Role | What they receive |
|---|---|---|
| Furosemide | Experimental | Diuretic Receives: Drug: Furosemide |
| Placebo | Placebo comparator | Normal saline Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients enrolled
Measured: 2 months period
Secondary outcomes (22)
Proportion of patients screened meeting eligibility criteria
Measured: 2 months
Proportion of eligible patients consenting to participate
Measured: 2 months
Proportion of patient receiving the allocated treatment
Measured: 2 months
Proportion of treated patients completing follow-up assessment
Measured: 2 months
Proportion of patient in which blinding was maintained throughout study
Measured: 2 months
Vital Signs
Change in vital signs immediately post-transfusion and at 6 hours post-transfusion
Measured: Baseline and 6 hours post transfusion
Positive end-expiratory pressure
For patients on mechanical ventilation pre-transfusion, change in positive end-expiratory pressure
Measured: Baseline and 6 hours post transfusion
Inspiratory oxygen
change in fraction of inspiratory oxygen at 6 hours post-transfusion
Measured: Baseline and 6 hours post transfusion
Incidence of TACO within 6 hours from completion of transfusion
Measured: within 6 hours
Severity of TACO-graded as per the Public Health Agency of Canada's Transfusion Transmitted Injuries Surveillance System
Measured: within 6 hours
Validation of TACO as per criteria adopted from the US Center for Disease Control
Measured: within 6 hours
Change in plasma brain natriuretic peptide(BNP)
Measured: 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)
Measured: Within 24 hours
Proportion of patients developing hyponatremia or hypokalemia by Day 1
Measured: By Day 1
Proportion of patients developing hypotension
Measured: Within 24 hours
Proportion of patients developing acute kidney injury
Measured: 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%
Measured: Within 24 hours
Need for inotropic support is defined as the initiation of a continuous infusion of dopamine, dobutamine, epinephrine, or norepinephrine
Measured: 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
Measured: Within 24 hours
Occurrence of acute coronary syndrome or new arrhythmia
Measured: within 7 days
Mortality during hospital stay
Measured: Upto 30 days
Length of hospital stay
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2016 (estimated)
- Study startJun 2016
- Primary completion17 Mar 2017
- Study completion15 Apr 2017
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 Transfusion-associated Circulatory OverloadStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- University Health Network, Toronto, Canadian Blood Services
- Responsible party
- Sponsor
- Investigators
- Jeannie Callum, MD, Principal investigator, Sunny Brook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02802696
- Sponsor's protocol ID
- 16-5032
- Status last verified
- Oct 2016
- First submitted
- 29 Feb 2016
- Last updated
- 26 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
AABB (2015) AABB Association Bulletin #15-02: Transfusion Associated Circulatory Overload (12/28/15). Vol. 2016,
Alam A, Lin Y, Lima A, Hansen M, Callum JL. The prevention of transfusion-associated circulatory overload. Transfus Med Rev. 2013 Apr;27(2):105-12. doi: 10.1016/j.tmrv.2013.02.001. Epub 2013 Mar 1.
PubMed 23465703Lieberman L, Maskens C, Cserti-Gazdewich C, Hansen M, Lin Y, Pendergrast J, Yi QL, Callum J. A retrospective review of patient factors, transfusion practices, and outcomes in patients with transfusion-associated circulatory overload. Transfus Med Rev. 2013 Oct;27(4):206-12. doi: 10.1016/j.tmrv.2013.07.002. Epub 2013 Sep 26.
PubMed 24075097Sarai M, Tejani AM. Loop diuretics for patients receiving blood transfusions. Cochrane Database Syst Rev. 2015 Feb 16;2015(2):CD010138. doi: 10.1002/14651858.CD010138.pub2.
PubMed 25685898
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02802696
- Acronym / sponsor ID
- 16-5032
- Keywords
- Transfusion, Transfusion Medicine, Diuretic
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- University Health Network, Toronto, Canadian Blood Services
- Study start
- Jun 2016
- Primary completion
- 17 Mar 2017 (actual)
- Study completion
- 15 Apr 2017 (actual)
- First posted
- 16 Jun 2016 (estimated)
- 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 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:
- Proportion of patients screened meeting eligibility criteria
- Proportion of eligible patients consenting to participate
- Proportion of consenting patients receiving the allocated treatment
- Proportion of treated patients completing follow-up assessment
- 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Furosemide | Experimental | Drug: FurosemideDiuretic |
| Placebo | Placebo comparator | Drug: Normal SalineNormal saline |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- Age ≥ 65 years.
- Receiving a single unit red blood cell transfusion
Key exclusion criteria (12 listed)
- 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);
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 |
|---|---|---|
| FurosemideAlso: LasixA 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. | Drug | Furosemide |
| Normal SalineAlso: 0.9% Sodium ChlorideA 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. | Drug | Placebo |
Primary outcome
Number of patients enrolled
Time frame: 2 months period
22 secondary outcomes
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
Positive end-expiratory pressure
Time frame: Baseline and 6 hours post transfusion
Inspiratory oxygen
Time frame: Baseline and 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.
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 26 Jun 2017.
- BackgroundAABB (2015) AABB Association Bulletin #15-02: Transfusion Associated Circulatory Overload (12/28/15). Vol. 2016,
- Background: PubMed 23465703Alam A, Lin Y, Lima A, Hansen M, Callum JL. The prevention of transfusion-associated circulatory overload. Transfus Med Rev. 2013 Apr;27(2):105-12. doi: 10.1016/j.tmrv.2013.02.001. Epub 2013 Mar 1.
- Background: PubMed 24075097Lieberman L, Maskens C, Cserti-Gazdewich C, Hansen M, Lin Y, Pendergrast J, Yi QL, Callum J. A retrospective review of patient factors, transfusion practices, and outcomes in patients with transfusion-associated circulatory overload. Transfus Med Rev. 2013 Oct;27(4):206-12. doi: 10.1016/j.tmrv.2013.07.002. Epub 2013 Sep 26.
- Background: PubMed 25685898Sarai M, Tejani AM. Loop diuretics for patients receiving blood transfusions. Cochrane Database Syst Rev. 2015 Feb 16;2015(2):CD010138. doi: 10.1002/14651858.CD010138.pub2.
- Individual participant dataSharing planned: Undecided
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.
Jeannie Callum, MD principal investigator
Sunny Brook Health Sciences Centre
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Furosemide and Normal Saline in people with Transfusion-associated Circulatory Overload, run by Sunnybrook Health Sciences Centre at 3 sites in Canada.
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 2 inclusion and 12 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 26 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Number of patients enrolled (time frame: 2 months period). 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 NCT02802696, 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 26 Jun 2017.