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Red Blood Cell Transfusion Thresholds and QOL in MDS

Red Blood Cell Transfusion Thresholds and QOL in MDS (EnhanceRBC): a Pilot, Feasibility Study

Status
UNKNOWN
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02099669
Acronym
EnhanceRBC
Enrollment
30
Registered
2014-03-31
Start date
2014-03-31
Completion date
2019-01-31
Last updated
2018-04-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Myelodysplastic Syndromes (MDS), Quality of Life, Red Blood Cell (RBC) Transfusions

Brief summary

Myelodysplastic syndromes (MDS) are bone marrow malignancies characterized by poor bone marrow function that may progress to acute myeloid leukemia. Many patients become red blood cell transfusion-dependent. Transfusion dependence is associated with inferior quality of life (QOL). However, the relationship between the degree of anemia and QOL is less clear. A commonly used transfusion strategy is to target the hemoglobin (Hb) in the range of 80-90 g/L (normal hemoglobin \> 120-130g/L). The question is: would a higher hemoglobin target lead to improvement in QOL despite the negative impact transfusion dependence may have on QOL (due to associated time commitments, expense, transfusion reactions etc). Several groups have prospectively shown that targeting hemoglobin levels of greater than 120 g/L (with hematopoietic growth factors (HGFs) and/or blood transfusions) or incremental increases of 15-20 g/L (with HGFs alone) were associated with improved QOL. The investigators MDS program has been conducting prospective assessments of QOL since 2007 in all registered and consented patients using a variety of validated questionnaires. Preliminary analysis (in 236 patients) revealed that, compared with an age-matched healthy general population, MDS patients have inferior QOL. Transfusion dependence and anemia were independently predictive of poor functioning, fatigue and decreased health utility. Furthermore, a hemoglobin level of ≥100 g/L seemed to be the key threshold for improvement in function and symptom scores. The investigators hypothesize that the target hemoglobins in transfusion dependent MDS patients are too low and this may account for their inferior quality of life. Our goal is to compare the effect on QOL of a restrictive strategy (which is the current standard of care), with a liberal transfusion strategy in a large randomized controlled trial of transfusion dependent MDS outpatients. Before embarking on such an endeavor, the investigators must first prove feasibility in a smaller pilot randomized controlled trial.

Detailed description

Myelodysplastic syndromes (MDS) are bone marrow malignancies characterized by poor bone marrow function that may progress to acute myeloid leukemia. Many patients become red blood cell transfusion-dependent. Transfusion dependence is associated with inferior quality of life (QOL). However, the relationship between the degree of anemia and QOL is less clear. A commonly used transfusion strategy is to target the hemoglobin (Hb) in the range of 80-90 g/L (normal hemoglobin \> 120-130g/L). The question is: would a higher hemoglobin target lead to improvement in QOL despite the negative impact transfusion dependence may have on QOL (due to associated time commitments, expense, transfusion reactions etc). Several groups have prospectively shown that targeting hemoglobin levels of greater than 120 g/L (with hematopoietic growth factors (HGFs) and/or blood transfusions) or incremental increases of 15-20 g/L (with HGFs alone) were associated with improved QOL. The investigators MDS program has been conducting prospective assessments of QOL since 2007 in all registered and consented patients using a variety of validated questionnaires. Preliminary analysis (in 236 patients) revealed that, compared with an age-matched healthy general population, MDS patients have inferior QOL. Transfusion dependence and anemia were independently predictive of poor functioning, fatigue and decreased health utility. Furthermore, a hemoglobin level of ≥100 g/L seemed to be the key threshold for improvement in function and symptom scores. The investigators hypothesize that the target hemoglobins in transfusion dependent MDS patients are too low and this may account for their inferior quality of life. Our goal is to compare the effect on QOL of a restrictive strategy (which is the current standard of care), with a liberal transfusion strategy in a large randomized controlled trial of transfusion dependent MDS outpatients. Before embarking on such an endeavor, the investigators must first prove feasibility in a smaller pilot randomized controlled trial.

Interventions

OTHERRed Blood Cell Transfusions

Sponsors

Princess Margaret Hospital, Canada
CollaboratorOTHER
Juravinski Cancer Center
CollaboratorOTHER
Sunnybrook Health Sciences Centre
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* All patients with MDS ≥18 years of age * Transfusion dependent: at least 1 transfusion per month in the last 8 weeks * Hb \<100g/L pre transfusion * Life expectancy \> 6 months

Exclusion criteria

* Unstable cardiac disease (Canadian Cardiovascular Society (CCS) III/IV angina or New York Heart Association (NYHA) III/IV congestive heart failure) requiring the transfusion target range to remain \>85-100 g/L at all times * ECOG ≥3 * Patients with red cell antibodies against high frequency antigens or multiple antibodies (would potentially delay finding blood) * Patients on ESA's or disease modifying agents (like azacitidine) for their MDS

Design outcomes

Primary

MeasureTime frameDescription
Percentage compliance of q2weekly hemoglobins3 monthsThe percentage compliance of q2weekly hemoglobins being within or above the target range of the RBC transfusion threshold assigned (after the 4 week run-in at study start as defined above). We will consider this study feasible and worthy of future development into a larger randomized trial (powered for QOL difference) if compliance is ≥70%. A compliance rate of 50-70%, would not exclude going forward with such an RCT but only after careful discussion and statistical planning

Secondary

MeasureTime frameDescription
Quality of life3 months• The magnitude of change in physical functioning, fatigue, dyspnea and global health scores on the EORTC QLQ-C30, calculated health utility on the EQ-5D and fatigue score on FACT-F comparing the 2 RBC transfusion thresholds above.
Adverse events3 months* The rate of transfusion reactions (as defined by TTISS (Transfusion Transmitted Injuries Surveillance System by Public Health Agency of Canada)) * Rate of adverse events such as cardiac events and thromboembolic events as per NCI CTCAE version 4.0 criteria
Alloimmunization rates3 monthsRate of alloimmunization to significant blood group antigens
Measures of feasibility3 months* Number of patients ineligible due to screen failure * Enrolment rates defined by the number of enrolled patients/month * Percentage compliance with QOL questionnaire completion at least 3 serial times * Other logistical issues related to protocol implementation, recruitment rates, randomization implementation strategy, data collection, patient tolerability of study schedule
Overall utilization of blood3 monthsHow many units of blood are required to maintain the hemoglobin threshold chosen
Time commitment3 months• The overall time commitment per group, measured as the time spent in transfusion medicine clinic
Hemosiderosis3 months• The impact on transfusion associated hemosiderosis rates and burdens (as measured by changes in ferritin levels and iron chelating medications)

Countries

Canada

Contacts

Primary ContactJennifer Gallagher
jennifer.gallagher@sunnybrook.ca
Backup ContactGeetha Yogendron

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 10, 2026