Practical Anemia Bundle for SusTained Blood Recovery

Phase 2

Completed

Conditions: Critical Illness
Anemia

Interventions: Drug: Iron Dextran
Drug: Erythropoietin (EPO)

Registration Number: NCT05167734

Lead Sponsor: Mayo Clinic

Brief Summary: The purpose of this study is to test a multi-faceted anemia treatment plan to reduce the severity of anemia and to promote hemoglobin and functional recovery in adults who have been in the intensive care unit (ICU).

Detailed Description: Anemia is common during critical illness and is associated with impaired outcomes during and after hospitalization. The goal of this investigation is to test a multi-faceted anemia prevention and targeted treatment bundle to attenuate anemia development and promote functional recovery in the setting of critical illness. Specifically, this will be a pragmatic phase II clinical trial of a multi-faceted anemia prevention and treatment bundle with 3 aspects (optimized phlebotomy practice, clinical decision support, targeted pharmacologic anemia treatment) assessing the impact of the intervention on hemoglobin concentrations (primary aim), transfusion utilization, and functional outcomes through 3 months after hospitalization.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

Inclusion Criteria

Provision of signed and dated informed consent form (may be completed by legal proxies for those patients unable to provide consent, i.e. sedation/intubation)
Stated willingness to comply with all study procedures and availability for the duration of the study, including follow-up assessments
Current ICU admission at Mayo Clinic Rochester with anticipated ICU duration >48 hours after enrollment
Current ICU duration < 7 days
Patients embedded in the local or regional Mayo Clinic Health System to facilitate post-hospitalization outcome assessment
Moderate-to-severe anemia (i.e. hemoglobin concentration < 10 g/dL) at the time of enrollment, with the hemoglobin concentration assessed no more than 24 hours prior to enrollment. If RBC transfusion has been administered between the qualifying hemoglobin assessment and enrollment, a repeat hemoglobin will be required prior to enrollment to ensure that it remains < 10 g/dL.

Exclusion Criteria

Recent or current IV iron or erythropoiesis stimulating agent (ESA) use (i.e. darbepoetin, Aranesp, erythropoietin, Epogen, Procrit, Retacrit) within 30 days of enrollment
Severe anemia prior to hospitalization (i.e. hemoglobin <9 g/dL within 90 days of admission)
Known allergic reactions to iron or EPO
Inability to complete outcome assessments (i.e. not expected to survive hospitalization, unable to make follow-up appointments, non-ambulatory, dementia or other severe cognitive impairment, visual impairment i.e. blind or legally blind)
Pregnancy or breastfeeding at time of enrollment
Inability to receive pharmacologic venous thromboembolic prophylaxis except in patients with recent surgical or gastrointestinal bleeding
Active or suspected thrombosis (i.e. deep venous thrombosis, pulmonary embolism, acute arterial thrombus within 3 months)
Uncontrolled sepsis (i.e. <48 hours of appropriate antimicrobial therapy and/or lack of definitive source control)
Having received ≥10 units of allogeneic RBCs in the 48 hours before enrollment
Acute coronary syndrome or ischemic stroke within 3 months
Weight less than 40 kg
Concerns with study enrollment expressed by the clinical team
Mechanical circulatory support devices

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anemia Treatment Bundle	Erythropoietin (EPO)	The intervention arm is multi-faceted with 3 primary components: 1) Optimized phlebotomy, defined by minimal volume draws and closed-loop blood sampling, all performed by a dedicated phlebotomy team independent from the treatment team; 2) Decision support aids, including visual and electronic alerts reminding the care team to minimize non-essential laboratory testing and mitigate patient-specific bleeding risk; and 3) Pharmacologic anemia treatment with a single dose of IV iron and/or subcutaneous erythropoietin (given immediately following enrollment) targeted to 2 broad groups: 1) anemias responsive to iron supplementation alone (i.e. acute blood loss, iron deficiency) and 2) anemias requiring erythropoietic stimulation (e.g. anemia of inflammation, anemia of renal disease).
Anemia Treatment Bundle	Iron Dextran	The intervention arm is multi-faceted with 3 primary components: 1) Optimized phlebotomy, defined by minimal volume draws and closed-loop blood sampling, all performed by a dedicated phlebotomy team independent from the treatment team; 2) Decision support aids, including visual and electronic alerts reminding the care team to minimize non-essential laboratory testing and mitigate patient-specific bleeding risk; and 3) Pharmacologic anemia treatment with a single dose of IV iron and/or subcutaneous erythropoietin (given immediately following enrollment) targeted to 2 broad groups: 1) anemias responsive to iron supplementation alone (i.e. acute blood loss, iron deficiency) and 2) anemias requiring erythropoietic stimulation (e.g. anemia of inflammation, anemia of renal disease).

Primary Outcome Measures

Name	Time	Method
Hemoglobin Concentrations	1 month post-hospitalization	Hemoglobin is a protein that cares oxygen through the body

Secondary Outcome Measures

Name	Time	Method
Hemoglobin Concentrations	Hospital discharge (approximately 1 month), 3 months post-hospitalization	Hemoglobin is a protein that cares oxygen through the body
Phlebotomy Practice-Blood Draws	Hospital discharge (approximately 1 month)	Number of times subjects have blood drawn
Phlebotomy Practice-Volume	Hospital discharge (approximately 1 month)	Total volume of phlebotomy blood draws
Unplanned Hospital Readmissions	3 months and 12-months post-hospitalization	Number of subjects to experience an unplanned hospital readmission
Mortality	3 months and 12-months post-hospitalization	Mortality from any cause
Adverse Events Post-enrollment	Hospital discharge (approximately 1 month), 3-months post-hospitalization	Venous thromboembolism, bloodstream infection, myocardial infarction, stroke
Accelerometry-measured Number of Steps Taken Per Day	1 and 3-months post-hospitalization	Home-based activity monitor daily step counts (optional, exploratory study component)
Accelerometry-measured Daily Maximum Step Cadence	1 month and 3 month post hospitalization	Actigraphy evaluated daily Max Step Cadence - i.e., steps per minute (optional, exploratory study endpoint)
Patient-Reported Quality of Life Measured by EuroQol (EQ-5D)	Hospital discharge (approximately 1 month), 1 month post-hospitalization, 3 months post-hospitalization	The EuroQol (EQ-5D) is a 5-item questionnaire that assess health-related quality of life over five different dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Total score ranges from 0 to 100, with higher scores indicating improved health.
Anemia-related Fatigue Measured by Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale	Hospital discharge (approximately 1 month), 1 month post-hospitalization, 3 months post-hospitalization	The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale is a 13-item questionnaire used to measure the severity of fatigue and its impact on daily activities. Each question is rated on a 4-point scale where 0 represents "very much" fatigued and 4 represents "not at all" fatigued. Total scores range from 0 to 52 with lower scores indicating greater fatigue.
6 Minute Walk Distance	1 and 3-months post-hospitalization	Distance walked in 6 minutes used to assess physical function after critical illness.
Cognitive Function After Critical Illness Assessed Using Montreal Cognitive Assessment (MoCA-BLIND)	1 and 3-months post-hospitalization	The Montreal Cognitive Assessment (MoCA-BLIND) score assesses cognitive impairment by a 30-item questionnaire that includes tests of orientation, attention, memory, language and visual-spatial skills. Possible scores range from 0 to 30, with higher scores indicating higher cognitive function. A final total score of 26 and above is considered normal.
Mental Health - Anxiety and Depression Measured Using the Hosptial Anxiety and Depression Scale (HADS)	1 and 3-months post-hospitalization	The Hospital Anxiety and Depression Scale (HADS) assesses a patient's anxiety and depression levels. Subject's answer 14 questions (7 for anxiety and 7 for depression). Each question is scored from 0-3. Total scores can range from 0 to 21 for either anxiety or depression, with higher scores indicating a presence of anxiety or depression.
Mental Health - Post-Traumatic Distress Using Impact of Events Scale-Revised (IES-R)	1 and 3-months post-hospitalization	The Impact of Events Scale-Revised (IES-R) is a self-reported questionnaire that measures the distress caused by traumatic events. Subjects respond to 22 questions using a 5-point scale ranging from 0 (not at all) to 4 (extremely). Total scores range from 0 to 88, with a higher score indicting the likely presence of post-traumatic stress disorder (PTSD).
Number of Participants With Allogeneic Red Blood Cell Transfusions	3-months post-hospitalization	Number (percentage) of patients transfused with allogeneic red blood cells
Number of Transfused Units of Allogeneic Red Blood Cells	3 months post hospitalization	Number of transfused units from hospital discharge through 3-months post-hospitalization