Practical Anemia Bundle for SusTained Blood Recovery

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Practical Anemia Bundle for SusTained Blood Recovery (PABST-BR) Clinical Trial

Conditions
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Anemia, Critical Illness

Intervention / Treatment
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* Drug: Iron Dextran
* Drug: Erythropoietin (EPO)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control (Standard of Care) Group<br>Subjects will receive standard clinical care for the treatment of anemia while in the ICU. | |
| Experimental: Anemia Treatment Bundle<br>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). | Drug: Iron Dextran<br>* 1000 mg IV<br>Drug: Erythropoietin (EPO)<br>* 40,000 units subcutaneous<br>* Other names: EPO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin concentrations | Mean difference in hemoglobin concentrations | 1 month post-hospitalization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin concentrations | Mean difference in hemoglobin concentrations | Hospital discharge (approximately 1 month) and 3 months post-hospitalization | 
| Phlebotomy practice | Number of times subjects have blood drawn and total phlebotomy volumes | Hospital discharge (approximately 1 month) | 
| Patient-Reported Quality of Life | Measured by patient-reported EuroQol (EQ-5D) questionnaire | Hospital discharge (approximately 1 month), 1 month post-hospitalization, 3 months post-hospitalization | 
| Anemia-related fatigue | Measured by patient-reported Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale (13 questions) | Hospital discharge (approximately 1 month), 1 month post-hospitalization, 3 months post-hospitalization | 
| 6 minute walk distance | Distance walked in 6 minutes used to assess physical function after critical illness. | 1 and 3-months post-hospitalization | 
| Cognitive function after critical illness | Montreal Cognitive Assessment (MoCA-BLIND) | 1 and 3-months post-hospitalization | 
| Mental Health - Anxiety and Depression | Hospital Anxiety and Depression Scale (HADS) | 1 and 3-months post-hospitalization | 
| Mental Health - Post-Traumatic Distress | Impact of Events Scale-Revised (IES-R) | 1 and 3-months post-hospitalization | 
| Allogeneic red blood cell transfusions | Proportion of patients transfused and number of transfused units | Hospital discharge (approximately 1 month) and 3-months post-hospitalization | 
| Unplanned hospital readmissions | Number of subjects to experience an unplanned hospital readmission | 12-months post-hospitalization | 
| Mortality | Mortality from any cause | 12-months post-hospitalization | 
| Adverse events post-enrollment | Venous thromboembolism, bloodstream infection, myocardial infarction, stroke | Hospital discharge (approximately 1 month) and 3-months post-hospitalization | 
| Actigraph activity expenditures | Actigraph activity monitor step counts and energy expenditure | 1 and 3-months post-hospitalization |