A Patient-centered Trial of a Process-of-care Intervention in Hospitalized AKI Patients: the COPE-AKI Trial

Study Overview
=================
Brief Summary
-----------------
The COPE-AKI study is a randomized, pragmatic, parallel-arm trial comparing a multimodal intervention to usual care on hospital-free days through 90 days of study follow up. The primary study hypothesis is that patients randomized to the intervention will have increased odds of more hospital-free days through 90 days (primary clinical) compared to those randomized to usual care. Key secondary hypotheses will investigate the impact of the intervention on rates of major adverse kidney events, rates of recurrent AKI, and changes in patient-reported outcomes. Participants (N=2145) will be allocated 1:1 to the intervention or usual care using a web-based system to maintain allocation concealment using stratified randomization with randomly permuted blocks. Randomization will be stratified by clinical site.

Detailed Description
-----------------
The primary study hypotheses for the COPE-AKI study are: compared to usual care, patients randomized to a multimodal intervention will have increased odds of more hospital-free days through 90 days (primary) and lower rates of major adverse kidney events (MAKE) at 180 days, lower rates of recurrent AKI at 180 days, and greater improvements in patient-reported outcomes over 90 days (secondary). The primary outcome is hospital-free days through 90 days of follow up, defined as 90 minus the number of calendar days in the hospital as either an inpatient or on observation status, based on the determination made by the corresponding hospital. Key secondary outcomes include: rates of MAKE (measured at 90, 180, and 365 days), rates of recurrent AKI (90, 180, and 365 days), and 4 patient-report outcomes: global health related quality of life, AKI-specific health related quality of life, provider interactions, and social support (30, 90, 180, 365 days). A multimodal process-of-care intervention that includes 1) study physician oversight and follow up care recommendations at the time of hospital discharge; 2) involvement of a nurse navigator to provide kidney-disease related education, coordinate care, and assess symptoms; and 3) pharmacist-led medication reconciliation and review. Participants in the usual care arm will be provided information about their kidney disease, nephrotoxins to be avoided, and the importance of follow up with a physician will be emphasized.

Official Title
-----------------
Caring for OutPatiEnts After Acute Kidney Injury (COPE-AKI) Trial

Conditions
-----------------
Acute Kidney Injury

Intervention / Treatment
-----------------
* Other: Study Physician/Advance Practice Provider
* Other: Nurse Navigator
* Other: Pharmacist
* Other: Patient Education


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged ≥ 18 years Kidney Disease Improving Global Outcomes (KDIGO) Stage 2/3 AKI with evidence of persistent AKI (defined as meeting Stage 2+ AKI for 2 consecutive days with serum creatinine concentration measurements >12 hours apart) Exclusion Criteria: AKI due to primary glomerulonephritis, renal vasculitis, or thrombotic microangiopathy Diagnosis of end-stage kidney disease (ESKD) at the time of admission, defined as: Baseline estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m2 Previous kidney transplant recipient On chronic dialysis Acute urinary obstruction with rapid kidney function improvement following relief of obstruction Index hospitalization involving nephrectomy Index hospitalization involving solid organ transplant or stem cell/bone marrow transplant Continued dialysis dependence at time of discharge Previous (within 6 months) or new referral to a nephrologist for care specifically for: Previous or new diagnosis of glomerulonephritis Primary electrolyte imbalance disorders unrelated to AKI (e.g., syndrome of inappropriate antidiuretic hormone secretion, Bartter syndrome) Active treatment for acute interstitial nephritis Non-kidney end-organ failure: Class IV congestive heart failure Decompensated cirrhosis with Model For End-Stage Liver Disease (MELD) > 30 or those with a diagnosis of hepatorenal syndrome by the clinical teams End-stage pulmonary disease (advanced stage chronic obstructive pulmonary disease, interstitial lung disease, cystic fibrosis, pulmonary hypertension) Metastatic malignancy or malignancy requiring active treatment (chemotherapy, immunotherapy), such as multiple myeloma Primary goal of care is palliation: life expectancy <6 months Pregnancy Vulnerable populations Persons incarcerated Persons institutionalized Inability to provide informed consent a. Impaired cognition as demonstrated by the Brief Confusion Assessment Method (bCAM) Concurrent enrollment in a separate greater than minimal risk interventional trial Inability to participate in either in-person or remote visits a. Inability to participate as determined by the research team at time of discharge based on disposition (vs uniform decision across site about exclusion based on SNF) Discharge to long-term acute care facility or other hospital-based location

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, pragmatic, parallel-arm kidney trial conducted to find out if an enhanced care team approach can improve a patient's outcomes after hospitalization with acute kidney injury (AKI). Participants (N=2145) will be allocated 1:1 to the intervention or usual care using a web-based system to maintain allocation concealment using stratified randomization with randomly permuted blocks. Randomization will be stratified by clinical site.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multimodal Process of Care Intervention<br>A multimodal process-of-care intervention that includes 1) study physician oversight and follow up care recommendations at the time of hospital discharge; 2) involvement of a nurse navigator to provide kidney-disease related education, coordinate care, and assess symptoms; and 3) pharmacist-led medication reconciliation and review. | Other: Study Physician/Advance Practice Provider<br>* The nephrologist and/or nephrology-associated advanced practice provider (APP) at each site will lead the intervention team for the duration of the study. The study physicians will fulfil two main roles: (a) Provide supervision to the rest of the study team and (b) conduct a discharge assessment to triage and make recommendations for follow-up care.<br>Other: Nurse Navigator<br>* The nurse navigator will be the primary contact for the participants assigned to the intervention group for the study. The navigator will obtain contact information, information about the patient's usual care providers and pharmacy, review medications, show the participant how to use the home blood pressure machine and scales and arrange for follow-up visits. The role of the nurse navigator will be to monitor the participant's medical condition; facilitate scheduling of needed medical follow-up including both routine (pre-scheduled) and ad hoc (urgent or emergency); enhance adherence with prescribed medical care and follow-up appointments; and serve as a resource to the patient to answer questions about their AKI-related management, facilitate medical and associated care and provide enhanced psychosocial support.<br>Other: Pharmacist<br>* The pharmacist will complete the medication reconciliation and medication regimen review per the predetermined checklist, via telemedicine if agreeable to the patient. The goal of the patient/caregiver-pharmacist interaction is to cover the following: avoidance of nephrotoxins when possible and appropriate, appropriate dosing of renally cleared drugs, review for drug-drug interactions, monitoring appropriate use of chronic medications, medication adherence, monitor for adverse drug reactions, evaluation of non-prescription medication use, medication/disease education and social support.<br>Other: Patient Education<br>* Written information about kidney disease, nephrotoxins to be avoided and importance/need for follow up with a physician will be provided.<br>|
| Active Comparator: Usual Care<br>After receiving the same written information about kidney disease, nephrotoxins to be avoided and importance/need for follow up with a physician as individuals randomized to the multimodal intervention arm, participants randomized to the control arm will receive usual care as specified by their treating providers and will not be followed by nurse navigator, pharmacist, or the study team. The only subsequent study-related activities will be the follow-up study visits for ascertainment of endpoints with the research coordinator. | Other: Patient Education<br>* Written information about kidney disease, nephrotoxins to be avoided and importance/need for follow up with a physician will be provided.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital-Free Days (HFDs) through day 90 | Hospital-free days through day 90 defined as 90 minus the number of calendar days in the hospital as either an inpatient or on observation status. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Major Adverse Kidney Events (MAKE) at 180 days | MAKE-180 composite outcome of death, dialysis and assessment of kidney function defined as: death within 180 days of index hospital discharge; need for dialysis at 180 days after index hospital discharge; or serum creatinine >2x baseline at 180 days after index hospital discharge | 180 days | 
| Recurrent Acute Kidney Injury (AKI) Hospitalization at 180 days | Episodes of recurrent AKI during subsequent all-cause hospitalizations will be adjudicated based on hospitalization data, defining recurrent episodes of AKI based on an increase in serum creatinine of >50% relative to the lowest-known value preceding or including the rehospitalization. | 180 days | 
| Change from baseline in Global Health-Related Quality of Life (HR-QoL) at 180 days. | HR-QOL will be assessed with the 10-item Patient-Reported Outcomes Measurement Information System (PROMIS) HRQoL measure. The PROMIS Global Health measures assess an individual's physical, mental, and social health. The measures are generic, rather than disease-specific, and often use an In General item context as it is intended to globally reflect individuals' assessment of their health. The adult PROMIS Global Health measure produces two scores: Physical Health and Mental Health, which are rescaled into a standardized score (T-score) with a mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean. A higher T-score represents more of the concept being measured. Thus, a person who has T-scores of 60 for the Global Physical Health or Global Mental Health scales is one standard deviation better (more healthy) than the general population. | 180 days | 
| Change from baseline in AKI-Specific Health-Related Quality of Life (HR-QoL) at 180 days. | AKI-Specific HR-QOL will be assessed with the 6-item Chronic Kidney Disease Quality of Life (CKD-QoL) measure. The CKD-QoL comprehensively represents CKD-specific quality of life and yields a single summary impact score. Norm-based scoring is used (linearly transformed to have a mean of 50 and an SD of 10) in which a higher score indicates worse QOL impact. | 180 days | 
| Change from baseline in Interactions with Providers at 180 days. | Provider interactions will be assessed with the 5-item Perceived Efficacy in Patient-Physician Interactions (PEPPI) and 8-item Client Satisfaction Questionnaire (CSQ-8) measures. The PEPPI provides a summary score ranging for 5 to 25 (25 = sighted patient self-efficacy). The CSQ-8 is a structured survey used to assess level of satisfaction with care. Items are scored on a Likert scale from 1 (low satisfaction) to 4 (high satisfaction) with different descriptors for each response point. Total scores range from 8 to 32, with higher scores indicating greater satisfaction. | 180 days | 
| Change from baseline in Social Support at 180 days. | Social support will be assessed with the 4-item PROMIS Emotional Support and 4-item PROMIS Instrumental Support short forms. The Emotional Support and Instrumental Support measures each produce a summary score, which are rescaled into a standardized score (T-score) with a mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean. A higher T-score represents more of the concept being measured. Thus, a person who has a T-score of 60 is one standard deviation better (more healthy) than the general population. | 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
acute kidney injury, process of care, acute renal failure, kidney failure, kidney damage, pragmatic, nurse navigator, pharmacist