Chronic Kidney Diseases
Conditions
Keywords
electronic health record, population health management, patient education, medication therapy management, electronic consultation, randomized controlled trial, pragmatic trial
Brief summary
As part of a 42-month pragmatic, cluster randomized trial in 1,650 primary care patients with high-risk Chronic Kidney Disease (CKD), the investigators will test the effectiveness of a multifaceted Electronic Health Record (EHR)-based Population Health Management (PHM) intervention that targets improvements in the delivery of evidence-based CKD care.
Detailed description
To test the effectiveness of a multifaceted Electronic Health Record (EHR)-based Population Health Management (PHM) intervention to improve the delivery of evidence-based Chronic Kidney Disease (CKD) care in patients with high-risk CKD. Investigators will perform a 42-month pragmatic, cluster randomized (at the practice level) controlled trial in 1,650 patients with high-risk CKD (as defined by validated risk prediction models or by current estimated Glomerular Filtration Rate (eGFR) value or recent decline in eGFR values) managed by their Primary Care Physicians (PCPs) to determine whether EHR-based PHM improves key processes of care and clinical outcomes. The investigators hypothesize that EHR-based PHM will improve hypertension control, use of renin angiotensin aldosterone system inhibitors (RAASi), and avoidance of renally contraindicated medications (Aim 1a-1c) and delay CKD progression (Aim 2). Investigators will also characterize the acceptability and experience of Primary Care Physicians (PCPs) in the intervention arm of the CKD PHM study (Aim 3).
Interventions
OTHEREHR-based PHM
An EHR in-basket message will be sent to the patient's PCP which identifies the patient's high-risk CKD status and indicates that the patient will receive: 1. Nephrologist led electronic consultation: review of the patient's EHR with recommendations sent to the PCP every \ 6 months, 2. Medication therapy management: PharmD led telephonic medication therapy management with the patient every \ 6 months, 3. and Nurse led CKD patient education, every \ 6-12 months unless the PCP opts the patient out of the interventions (by responding to the EHR in-basket message and providing an opt-out reason or requesting an office consultation with nephrology).
OTHERUsual Care
Patients in the usual care arm will continue to receive CKD care guided by their PCPs as per usual care practices (i.e., specialty consultation, pharmacotherapy, nurse education, etc. may be ordered by the PCP according to their usual practice).
Sponsors
Vanderbilt University Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
outcomes are ascertained by data programmers who are blinded to study arm assignment
Intervention model description
Cluster randomized controlled trial with randomization occurring at the Primary Care Physician practice level
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
for PCPs: presence of an ambulatory continuity clinic in the University of Pittsburgh Medical Center (UPMC) community medicine practice. Inclusion criteria for patients: 1. age greater than or equal to 18, and less than or equal to 85 2. most recent eGFR less than 60 ml/min/yr 3. established care with UPMC PCP 4. high risk CKD based on validated external and internal risk prediction models or severe reduction in eGFR, or substantial loss in eGFR in prior 18 months.
Exclusion criteria
for PCPs: none
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal Failure Event Defined as Greater Than or Equal to 40% Decline in Estimated Glomerular Filtration Rate (eGFR) or Occurrence of End Stage Renal Disease (ESRD) | Time to event analysis - until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months). Cumulative % at 24 months reported | The outcome measure is occurrence of renal failure event and is defined as a greater than or equal to 40% decline in eGFR or occurrence of End Stage Renal Disease. The 40% decline in renal failure is a well accepted endpoint for renal failure in clinical trials and is approved by the FDA. eGFR decline will be adjudicated based on the baseline creatinine and eGFR determined from the CKD-epidemiology (CKD-EPI) equation and measured routinely in clinical practice. All eGFR values within 6-month windows will be averaged to account for ascertainment bias, and analyzed using discrete-time survival approach using generalized linear mixed model. ESRD will be defined as an eGFR less than or equal to 10ml/min, or starting of renal replacement therapy (dialysis or kidney transplant) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) Exposure Days Per Year | Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months) | Will be determined by active use of an Angiotensin-Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) based on the EHR medication list at each outpatient encounter (cumulative person-time exposure during the study). Reported as exposure days per year rate for each arm |
| Medication Safety: Non-Steroidal Anti-inflammatory Drugs (NSAIDS) Exposure Days Per Year | Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months) | Investigators will examine the rates of use of several high-risk medications that can be associated with adverse outcomes in progressive CKD. Medication exposure will be determined by presence of the specified medication on the patient's EHR medication list at each outpatient encounter (cumulative person-time exposure during the study). Reported as exposure days per year rate for each arm NSAIDS use will be examined for all study patients |
| Medication Safety: Glyburide Exposure Days Per Year | Time to event analysis - Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period(max 39 months) | Investigators will examine the rates of use of several high-risk medications that can be associated with adverse outcomes in progressive CKD. Medication exposure will be determined by presence of the specified medication on the patient's EHR medication list at each outpatient encounter (cumulative person-time exposure during the study). Reported as Exposure days per year rate for each arm Glyburide use will be examined for all study patients with diabetes at baseline |
| Medication Safety: Metformin Exposure Days Per Year | Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months) | Investigators will examine the rates of use of several high-risk medications that can be associated with adverse outcomes in progressive CKD. Medication exposure will be determined by presence of the specified medication on the patient's EHR medication list at each outpatient encounter (cumulative person-time exposure during the study). Reported as Exposure days per year rate for each arm Use of metformin will be examined for all study patients with diabetes at baseline and eGFR less than 30 |
| Medication Safety: Gemfibrozil Exposure Days | Time to event analysis - Follow up duration until primary outcome or a competing event was achieved or until end of intervention period (max 39 months) | We will examine the rate of use of gemfibrozil among those with eGFR\<30 at baseline |
| Hypertension (HTN) Control Outcome | Time to event analysis - until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months) | HTN control is defined as achieved BP\<140/90mmHg. Outpatient, sitting Blood Pressure (BP) values measured during each outpatient encounter and recorded in the EHR. All BPs within a 6-month window are averaged to account for ascertainment bias and then analyzed using generalized linear mixed model for average BP as binary outcome. Result is reported as log-odds per month slope for each arm. Higher log-odds indicates higher rate of BP control |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subgroup Analysis: Use of Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) (Outcome 3) in Participants With UACR ≥300 mg/g | Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months) | Outcome 3 will be repeated in the subgroup of participants receiving RAASi who have macroalbuminuria, RAASi use will be determined by active use of an Angiotensin-Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) based on the EHR medication list at each outpatient encounter (cumulative person-time exposure during the study). |
| Hypertension (HTN) Control for Achieved BP <130/80 mm Hg | Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months) | HTN control is defined as achieved BP\<130/80mmHg. Outpatient, sitting Blood Pressure (BP) values measured during each outpatient encounter and recorded in the EHR. All BPs within a 6-month window are averaged to account for ascertainment bias and then analyzed using generalized linear mixed model for average BP as binary outcome. Result is reported as log-odds per month slope for each arm. Higher log-odds indicates higher rate of BP control |
Countries
United States
Participant flow
Pre-assignment details
18,157 participants from 101 practices underwent initial screening. Out of these 1,803 from 9 practices were eligible at initial screening, which included 874 (from 50 practices) in control arm, and 929 (from 4 practices) in intervention arm. Patients who had confirmed eligibility after initial screening and had a PCP appointment within 1 year of eligibility screening were enrolled. In intervention group, patients or PCPs who opted-out at this stage were not enrolled
Participants by arm
| Arm | Count |
|---|---|
| Intervention Arm Patients will receive a care bundle
EHR-based PHM: An EHR in-basket message will be sent to the patient's PCP which identifies the patient's high-risk CKD status and indicates that the patient will receive:
1. Nephrologist led electronic consultation: review of the patient's EHR with recommendations sent to the PCP every \
6 months,
2. Medication therapy management: PharmD led telephonic medication therapy management with the patient every \
6 months,
3. and Nurse led CKD patient education, every \
6-12 months
unless the PCP opts the patient out of the interventions (by responding to the EHR in-basket message and providing an opt-out reason or requesting an office consultation with nephrology). | 754 |
| Intervention Arm Patients will receive a care bundle
EHR-based PHM: An EHR in-basket message will be sent to the patient's PCP which identifies the patient's high-risk CKD status and indicates that the patient will receive:
1. Nephrologist led electronic consultation: review of the patient's EHR with recommendations sent to the PCP every \
6 months,
2. Medication therapy management: PharmD led telephonic medication therapy management with the patient every \
6 months,
3. and Nurse led CKD patient education, every \
6-12 months
unless the PCP opts the patient out of the interventions (by responding to the EHR in-basket message and providing an opt-out reason or requesting an office consultation with nephrology). | 48 |
| Usual Care Patients in the usual care arm will continue to receive CKD care guided by their PCPs as per usual care practices (i.e., specialty consultation, pharmacotherapy, nurse education, etc. may be ordered by the PCP according to their usual practice).
Usual Care: Patients in the usual care arm will continue to receive CKD care guided by their PCPs as per usual care practices (i.e., specialty consultation, pharmacotherapy, nurse education, etc. may be ordered by the PCP according to their usual practice). | 842 |
| Usual Care Patients in the usual care arm will continue to receive CKD care guided by their PCPs as per usual care practices (i.e., specialty consultation, pharmacotherapy, nurse education, etc. may be ordered by the PCP according to their usual practice).
Usual Care: Patients in the usual care arm will continue to receive CKD care guided by their PCPs as per usual care practices (i.e., specialty consultation, pharmacotherapy, nurse education, etc. may be ordered by the PCP according to their usual practice). | 50 |
| Total | 1,694 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 142 | 130 |
| Overall Study | Medical management without dialysis | 37 | 1 |
Baseline characteristics
| Characteristic | Intervention Arm | Usual Care | Total |
|---|---|---|---|
| Age, Continuous | 73.8 years STANDARD_DEVIATION 9.1 | 73.4 years STANDARD_DEVIATION 8.8 | 73.6 years STANDARD_DEVIATION 8.9 |
| Diastolic Blood Pressure | 73.9 mmHg STANDARD_DEVIATION 10.4 | 74.4 mmHg STANDARD_DEVIATION 10.8 | 74.1 mmHg STANDARD_DEVIATION 10.6 |
| eGFR CKD-EPI | 37.1 ml/min/1.73m^2 STANDARD_DEVIATION 7.9 | 36.6 ml/min/1.73m^2 STANDARD_DEVIATION 7.9 | 36.8 ml/min/1.73m^2 STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 748 Participants | 831 Participants | 1579 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 51 Participants | 76 Participants | 127 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) White | 696 Participants | 753 Participants | 1449 Participants |
| Region of Enrollment United States | 754 participants | 842 participants | 1596 participants |
| Serum Creatinine | 1.7 mg/dL STANDARD_DEVIATION 0.4 | 1.7 mg/dL STANDARD_DEVIATION 0.4 | 1.7 mg/dL STANDARD_DEVIATION 0.4 |
| Sex: Female, Male Female | 409 Participants | 519 Participants | 928 Participants |
| Sex: Female, Male Male | 345 Participants | 323 Participants | 668 Participants |
| Systolic Blood Pressure | 131.1 mmHg STANDARD_DEVIATION 16.6 | 131.6 mmHg STANDARD_DEVIATION 17.2 | 131.4 mmHg STANDARD_DEVIATION 16.9 |
| Urine Albumin-creatinine ratio | 86.0 UACR mg/g | 84.6 UACR mg/g | 85.0 UACR mg/g |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 142 / 754 | 130 / 842 |
| other Total, other adverse events | 59 / 754 | 77 / 842 |
| serious Total, serious adverse events | 18 / 754 | 21 / 842 |
Outcome results
Primary
Renal Failure Event Defined as Greater Than or Equal to 40% Decline in Estimated Glomerular Filtration Rate (eGFR) or Occurrence of End Stage Renal Disease (ESRD)
The outcome measure is occurrence of renal failure event and is defined as a greater than or equal to 40% decline in eGFR or occurrence of End Stage Renal Disease. The 40% decline in renal failure is a well accepted endpoint for renal failure in clinical trials and is approved by the FDA. eGFR decline will be adjudicated based on the baseline creatinine and eGFR determined from the CKD-epidemiology (CKD-EPI) equation and measured routinely in clinical practice. All eGFR values within 6-month windows will be averaged to account for ascertainment bias, and analyzed using discrete-time survival approach using generalized linear mixed model. ESRD will be defined as an eGFR less than or equal to 10ml/min, or starting of renal replacement therapy (dialysis or kidney transplant)
Time frame: Time to event analysis - until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months). Cumulative % at 24 months reported
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Arm | Renal Failure Event Defined as Greater Than or Equal to 40% Decline in Estimated Glomerular Filtration Rate (eGFR) or Occurrence of End Stage Renal Disease (ESRD) | 9.7 percent |
| Usual Care | Renal Failure Event Defined as Greater Than or Equal to 40% Decline in Estimated Glomerular Filtration Rate (eGFR) or Occurrence of End Stage Renal Disease (ESRD) | 10.9 percent |
p-value: 0.8295% CI: [0.67, 1.38]Mixed Models Analysis
Secondary
Hypertension (HTN) Control Outcome
HTN control is defined as achieved BP\<140/90mmHg. Outpatient, sitting Blood Pressure (BP) values measured during each outpatient encounter and recorded in the EHR. All BPs within a 6-month window are averaged to account for ascertainment bias and then analyzed using generalized linear mixed model for average BP as binary outcome. Result is reported as log-odds per month slope for each arm. Higher log-odds indicates higher rate of BP control
Time frame: Time to event analysis - until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Intervention Arm | Hypertension (HTN) Control Outcome | 0.011 log-odds per month slope |
| Usual Care | Hypertension (HTN) Control Outcome | 0.0005 log-odds per month slope |
95% CI: [-0.008, 0.029]
Secondary
Medication Safety: Gemfibrozil Exposure Days
We will examine the rate of use of gemfibrozil among those with eGFR\<30 at baseline
Time frame: Time to event analysis - Follow up duration until primary outcome or a competing event was achieved or until end of intervention period (max 39 months)
Population: Although Gemfibrozil was a pre-specified secondary outcome, it was excluded from analyses since among those with eGFR\<30 at baseline, active use was found only in 1 patient control arm) and there is no statistically meaningful way of analyzing this
Secondary
Medication Safety: Glyburide Exposure Days Per Year
Investigators will examine the rates of use of several high-risk medications that can be associated with adverse outcomes in progressive CKD. Medication exposure will be determined by presence of the specified medication on the patient's EHR medication list at each outpatient encounter (cumulative person-time exposure during the study). Reported as Exposure days per year rate for each arm Glyburide use will be examined for all study patients with diabetes at baseline
Time frame: Time to event analysis - Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period(max 39 months)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Intervention Arm | Medication Safety: Glyburide Exposure Days Per Year | 2.4 exposure days per year |
| Usual Care | Medication Safety: Glyburide Exposure Days Per Year | 2.0 exposure days per year |
95% CI: [0.03, 53.78]
Secondary
Medication Safety: Metformin Exposure Days Per Year
Investigators will examine the rates of use of several high-risk medications that can be associated with adverse outcomes in progressive CKD. Medication exposure will be determined by presence of the specified medication on the patient's EHR medication list at each outpatient encounter (cumulative person-time exposure during the study). Reported as Exposure days per year rate for each arm Use of metformin will be examined for all study patients with diabetes at baseline and eGFR less than 30
Time frame: Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Intervention Arm | Medication Safety: Metformin Exposure Days Per Year | 17.8 exposure days per year |
| Usual Care | Medication Safety: Metformin Exposure Days Per Year | 16.0 exposure days per year |
95% CI: [0.12, 9.96]
Secondary
Medication Safety: Non-Steroidal Anti-inflammatory Drugs (NSAIDS) Exposure Days Per Year
Investigators will examine the rates of use of several high-risk medications that can be associated with adverse outcomes in progressive CKD. Medication exposure will be determined by presence of the specified medication on the patient's EHR medication list at each outpatient encounter (cumulative person-time exposure during the study). Reported as exposure days per year rate for each arm NSAIDS use will be examined for all study patients
Time frame: Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Intervention Arm | Medication Safety: Non-Steroidal Anti-inflammatory Drugs (NSAIDS) Exposure Days Per Year | 5.3 exposure days per year |
| Usual Care | Medication Safety: Non-Steroidal Anti-inflammatory Drugs (NSAIDS) Exposure Days Per Year | 6.7 exposure days per year |
95% CI: [0.51, 1.25]
Secondary
Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) Exposure Days Per Year
Will be determined by active use of an Angiotensin-Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) based on the EHR medication list at each outpatient encounter (cumulative person-time exposure during the study). Reported as exposure days per year rate for each arm
Time frame: Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Intervention Arm | Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) Exposure Days Per Year | 196.8 exposure days per year |
| Usual Care | Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) Exposure Days Per Year | 163.1 exposure days per year |
95% CI: [1.02, 1.43]
Other Pre-specified
Hypertension (HTN) Control for Achieved BP <130/80 mm Hg
HTN control is defined as achieved BP\<130/80mmHg. Outpatient, sitting Blood Pressure (BP) values measured during each outpatient encounter and recorded in the EHR. All BPs within a 6-month window are averaged to account for ascertainment bias and then analyzed using generalized linear mixed model for average BP as binary outcome. Result is reported as log-odds per month slope for each arm. Higher log-odds indicates higher rate of BP control
Time frame: Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Intervention Arm | Hypertension (HTN) Control for Achieved BP <130/80 mm Hg | 0.086 log-odds per month slope |
| Usual Care | Hypertension (HTN) Control for Achieved BP <130/80 mm Hg | 0.079 log-odds per month slope |
Other Pre-specified
Subgroup Analysis: Use of Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) (Outcome 3) in Participants With UACR ≥300 mg/g
Outcome 3 will be repeated in the subgroup of participants receiving RAASi who have macroalbuminuria, RAASi use will be determined by active use of an Angiotensin-Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) based on the EHR medication list at each outpatient encounter (cumulative person-time exposure during the study).
Time frame: Time to event analysis- Follow-up duration until primary outcome or a competing event (death, medication management without dialysis, being moved to hospice care) was achieved or until the end of intervention period (max 39 months)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Intervention Arm | Subgroup Analysis: Use of Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) (Outcome 3) in Participants With UACR ≥300 mg/g | 177.5 medication exposure days per year |
| Usual Care | Subgroup Analysis: Use of Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) (Outcome 3) in Participants With UACR ≥300 mg/g | 222.5 medication exposure days per year |