Ignite Creation Date:
2024-05-05 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00170183
Status:
COMPLETED
Last Update Posted:
2009-11-16
First Post:
2005-09-13
Brief Title:
Brain Natriuretic Peptide BNP to Preserve Renal Function in Hospitalized Patients With Heart Failure
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
BNP as Adjuvant Therapy to Preserve Renal Function and Facilitate Diuresis in Hospitalized Patients With Heart Failure
Status:
COMPLETED
Status Verified Date:
2009-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Patients hospitalized for treatment of decompensated heart failure CHF are at risk for prolonged length of stay LOS and frequent readmissions Renal dysfunction and diuretic resistance contribute to this risk particularly if renal dysfunction worsens during CHF treatment Brain natriuretic peptide BNP is a hormone of myocardial cell origin with well-defined physiological effects which include arterial and venous vasodilation suppression of adverse neurohumoral systems and favorable effects on renal hemodynamics and sodium excretion Recombinant human BNP Natrecor is approved by the FDA for treatment of decompensated CHF as it has been demonstrated to lower filling pressures and improve symptoms While clinical trials and the FDA support the use of BNP as adjuvant therapy in decompensated CHF the extent of its efficacy in improving non-hemodynamic CHF parameters has not been fully defined
The objective of this clinical practice protocol is to determine whether use of BNP in addition to standard therapy will preserve renal function and facilitate diuresis in patients with CHF and mild-moderate renal impairment creatinine clearance 20 but 60 mlmin as compared to standard therapy alone Patients admitted to the Mayo Heart Failure Service who meet entrance criteria will be randomized to standard clinical practice with or without a 48 hour infusion of BNP
The primary endpoints will be indices of renal function and diuretic response at 1 2 and 3 days and at discharge Secondary endpoints will be neurohumoral function LOS and 30-day readmission rate
The objective of this clinical practice protocol is to determine whether use of BNP in addition to standard therapy will preserve renal function and facilitate diuresis in patients with CHF and mild-moderate renal impairment creatinine clearance 20 but 60 mlmin as compared to standard therapy alone Patients admitted to the Mayo Heart Failure Service who meet entrance criteria will be randomized to standard clinical practice with or without a 48 hour infusion of BNP
The primary endpoints will be indices of renal function and diuretic response at 1 2 and 3 days and at discharge Secondary endpoints will be neurohumoral function LOS and 30-day readmission rate
Detailed Description:
Hypothesis
The objective of this clinical practice protocol is to determine whether use of BNP in addition to standard therapy will preserve renal function and facilitate diuresis in patients with CHF and renal impairment as compared to standard therapy alone The study is targeted at patients with mild to moderate renal dysfunction with adequate blood pressure who do not require inotropic therapy and are not felt to need intravenous vasodilator therapy for acute symptom control Patients will be randomized on admission to the heart failure service and prior to initiation of therapy Patients who receive initial therapy in the emergency department will be eligible but the therapy given in the emergency department will be recorded
Inclusion criteria
Clinical diagnosis of class III-IV CHF requiring hospitalization for treatment of CHF
Mild - moderate renal insufficiency 20 Creatinine Clearance 60 mlmin as calculated by the Cockcroft-Gault formula
Systolic BP 90
Stable cardiac rhythm
Unlikely to require cardiac catheterization
Exclusion criteria
Inability to give informed consent
New onset atrial fibrillation with rapid ventricular response HR 110 bpm
Active ischemia
Known or suspected stenotic valve disease
Acute clinical need for intravenous vasodilator including BNP therapy Severely symptomatic despite rest oxygen initial standard therapy
Primary reason for admission other than treatment of decompensated CHF rhythm device other medical problem
Primary Endpoints
1 Creatinine Creatinine Clearance at 123 days and at discharge
2 Wt loss at 123 days and at discharge
3 Fluid balance at 123 days and at discharge
4 Use of advanced therapy for diuretic resistance inotropes renal dopamine ultrafiltration dialysis
5 Meets criteria for diuretic resistance as defined in standardized diuretic protocol
Secondary Endpoints
1 LOS
2 30 day readmission for CHF hospital records V Mayo and patient phone call at 30 days
3 Plasma renin activity aldosterone ANP BNP N-proBNP Angiotensin II cGMP ET Cystatin C at baseline and just prior to end BNP infusion BNP group or at 48 hours after entry standard care group
Cockcroft-Gault Formula Weight in Kg Creatinine in mgdL - Use estimated Dry Weight Men Crt Cl 140-AgeWeight 72Crt Women Crt Cl 085 140-AgeWeight 72Crt
Power calculationSample size
We tabulated the HF hospital service profile in regards to renal function during a three-month period from May-July 2002 where 140 patients were admitted to the CHF service Data to calculate creatinine clearance was not available from this data base Mild-moderate renal dysfunction was characterized by creatinine of 14 - 30 mgdL and was present in 60 43 patients This likely represents a significant underestimation of those patients eligible for the study as our patients are elderly where creatinines 14 mgdL often correlate to creatinine clearances in the 20-60 range In the 60 patients with creatinines of 14-30 mgdL the mean change in creatinine during the hospitalization was 0022 or - 0377 mgdL Using this change as that expected in the standard therapy group enrolling 52 patients per treatment group n104 total would provide 80 power significance level of 005 to detect a change of 0222 mgdL in mean creatinine from 0022 to -0200 Using creatinine the 0222 mgdL change represents an effect size of 058 If one allocates representative weights and ages to the creatinines at admission and discharge and calculates the mean change in creatinine clearance a value of 154 or - 651 mlmin is obtained In this case a difference of 5 mlmin in the mean change in creatinine clearance between standard therapy and treated groups would represent a somewhat higher treatment effect 0768 indicating more than adequate power to detect a difference of 5 mlmin in the mean change in creatinine clearance between the two groups
Randomization
Patients will be randomized 11 standard therapy to BNP standard therapy Randomization will be stratified by creatinine clearance with two groups 20-39 mlmin and 40-59 mlmin
Analysis
Primary endpoints Mean change in creatinine creatinine clearance fluid balance and body weight will be calculated at 1 2 3 days and at discharge and compared between the BNP and standard therapy groups Percent patients meeting criteria for diuretic resistance and percent patients receiving advanced therapy for diuretic resistance in the two groups will be compared All data will be analyzed by intention to treat and by received active therapy for full 48 hours
Secondary endpoints Mean length of stay and readmission rate will be compared between the two groups Differences between groups will be compared by Students unpaired t test for continuous variables and Fischers exact test for nominal variables Data entry will be the duty of the nurse coordinator and will utilize both paper and an electronic case report form currently used by the CV studies unit The Investigators will utilize the Center for Patient Oriented Research for consultation in setting up the analyses
Recruitment potential
560 patientsyear admitted to CHF service If 46 have crt creatinine clearance 20-59 mlmin 257 patients1 year If 50 eligible patients enrolled 129 patients1 year If 40 eligible patients enrolled 103 patients1 year If 30 eligible patients enrolled 77 patients1 year
BNP therapy - in treatment arm only 2 ugkg bolus and 001 ugkgmin x 48 hours as long as Systolic BP SBP 90 and no symptoms thought related to decreased BP If SBP 90 and asymptomatic- dc infusion 250 cc NS resume at 0007 ugkgmin no bolus once BP 90 If SBP 90 and symptomatic - dc infusion 250 cc NS bolus Trendlenberg do not restart
Standard therapy to be used in both arms
ACE inhibitorsAngiotensin Receptor Blockers - initiate or adjust per clinical judgement
Digoxin - per clinical judgement
HydralazineIsordil - per clinical judgement
CoumadinAspirin - per clinical judgement
Beta Blockers - per clinical judgement
Calcium channel blockers - per clinical judgement
Non-cardiac meds - per clinical judgement
Spironolactone
1 already on - continue at current dose or dc as appropriate
2 already on - increase at dc if clinically indicated
3 not on - add at dc if clinically indicated
Other diuretic - discontinue and follow algorithm
Diet - 2 gm NaCl and 15 Liter total fluid restriction
Daily weights same scale
Accurate I and O
Oxygen - per clinical judgement
Diuretic therapy - Standardized Diuretic Algorithm based on initial creatinine clearance see below BNP must be started within 1-2 hours of randomization Diuretics will be started at 1 hour after start of the BNP infusion in BNP group Diuretics can be started immediately after randomization in the standard therapy group The study period is considered to start with initiation of BNP BNP group or diuretics Standard therapy group
Laboratory monitoring
Standard clinical care which includes daily electrolyte panel creatinine blood urea nitrogen sodium potassium Humoral function BNP ANP PRA Aldosterone ET N-proBNP Angiotensin II cGMP at baseline and prior to end of Natrecor infusion research labs Twenty ml of blood in standard EDTA tube and five ml of blood in EDTA tube with ACE inhibitor will be needed per blood draw
Vitals monitoring
Standard clinical care which includes established nursing protocols for use of BNP infusion on telemetry Introduction of BNP into clinical practice was piloted in the CCU and then on the cardiology telemetry units 4 Domatilla and 4 Joesph by the CHF group and is now standard clinical practice on these floors
Diuretic Algorithm
Initial dosing and subsequent dosing of diuretics are to follow the diuretic algorithm outlined below Can substitute bumex 1 mg bumex 40 mg furosemide Can delay progression to next level if within 10 of goal fluid balanceweight Clinician may use fluid balance OR weight to make decisions regarding progression to next level
The objective of this clinical practice protocol is to determine whether use of BNP in addition to standard therapy will preserve renal function and facilitate diuresis in patients with CHF and renal impairment as compared to standard therapy alone The study is targeted at patients with mild to moderate renal dysfunction with adequate blood pressure who do not require inotropic therapy and are not felt to need intravenous vasodilator therapy for acute symptom control Patients will be randomized on admission to the heart failure service and prior to initiation of therapy Patients who receive initial therapy in the emergency department will be eligible but the therapy given in the emergency department will be recorded
Inclusion criteria
Clinical diagnosis of class III-IV CHF requiring hospitalization for treatment of CHF
Mild - moderate renal insufficiency 20 Creatinine Clearance 60 mlmin as calculated by the Cockcroft-Gault formula
Systolic BP 90
Stable cardiac rhythm
Unlikely to require cardiac catheterization
Exclusion criteria
Inability to give informed consent
New onset atrial fibrillation with rapid ventricular response HR 110 bpm
Active ischemia
Known or suspected stenotic valve disease
Acute clinical need for intravenous vasodilator including BNP therapy Severely symptomatic despite rest oxygen initial standard therapy
Primary reason for admission other than treatment of decompensated CHF rhythm device other medical problem
Primary Endpoints
1 Creatinine Creatinine Clearance at 123 days and at discharge
2 Wt loss at 123 days and at discharge
3 Fluid balance at 123 days and at discharge
4 Use of advanced therapy for diuretic resistance inotropes renal dopamine ultrafiltration dialysis
5 Meets criteria for diuretic resistance as defined in standardized diuretic protocol
Secondary Endpoints
1 LOS
2 30 day readmission for CHF hospital records V Mayo and patient phone call at 30 days
3 Plasma renin activity aldosterone ANP BNP N-proBNP Angiotensin II cGMP ET Cystatin C at baseline and just prior to end BNP infusion BNP group or at 48 hours after entry standard care group
Cockcroft-Gault Formula Weight in Kg Creatinine in mgdL - Use estimated Dry Weight Men Crt Cl 140-AgeWeight 72Crt Women Crt Cl 085 140-AgeWeight 72Crt
Power calculationSample size
We tabulated the HF hospital service profile in regards to renal function during a three-month period from May-July 2002 where 140 patients were admitted to the CHF service Data to calculate creatinine clearance was not available from this data base Mild-moderate renal dysfunction was characterized by creatinine of 14 - 30 mgdL and was present in 60 43 patients This likely represents a significant underestimation of those patients eligible for the study as our patients are elderly where creatinines 14 mgdL often correlate to creatinine clearances in the 20-60 range In the 60 patients with creatinines of 14-30 mgdL the mean change in creatinine during the hospitalization was 0022 or - 0377 mgdL Using this change as that expected in the standard therapy group enrolling 52 patients per treatment group n104 total would provide 80 power significance level of 005 to detect a change of 0222 mgdL in mean creatinine from 0022 to -0200 Using creatinine the 0222 mgdL change represents an effect size of 058 If one allocates representative weights and ages to the creatinines at admission and discharge and calculates the mean change in creatinine clearance a value of 154 or - 651 mlmin is obtained In this case a difference of 5 mlmin in the mean change in creatinine clearance between standard therapy and treated groups would represent a somewhat higher treatment effect 0768 indicating more than adequate power to detect a difference of 5 mlmin in the mean change in creatinine clearance between the two groups
Randomization
Patients will be randomized 11 standard therapy to BNP standard therapy Randomization will be stratified by creatinine clearance with two groups 20-39 mlmin and 40-59 mlmin
Analysis
Primary endpoints Mean change in creatinine creatinine clearance fluid balance and body weight will be calculated at 1 2 3 days and at discharge and compared between the BNP and standard therapy groups Percent patients meeting criteria for diuretic resistance and percent patients receiving advanced therapy for diuretic resistance in the two groups will be compared All data will be analyzed by intention to treat and by received active therapy for full 48 hours
Secondary endpoints Mean length of stay and readmission rate will be compared between the two groups Differences between groups will be compared by Students unpaired t test for continuous variables and Fischers exact test for nominal variables Data entry will be the duty of the nurse coordinator and will utilize both paper and an electronic case report form currently used by the CV studies unit The Investigators will utilize the Center for Patient Oriented Research for consultation in setting up the analyses
Recruitment potential
560 patientsyear admitted to CHF service If 46 have crt creatinine clearance 20-59 mlmin 257 patients1 year If 50 eligible patients enrolled 129 patients1 year If 40 eligible patients enrolled 103 patients1 year If 30 eligible patients enrolled 77 patients1 year
BNP therapy - in treatment arm only 2 ugkg bolus and 001 ugkgmin x 48 hours as long as Systolic BP SBP 90 and no symptoms thought related to decreased BP If SBP 90 and asymptomatic- dc infusion 250 cc NS resume at 0007 ugkgmin no bolus once BP 90 If SBP 90 and symptomatic - dc infusion 250 cc NS bolus Trendlenberg do not restart
Standard therapy to be used in both arms
ACE inhibitorsAngiotensin Receptor Blockers - initiate or adjust per clinical judgement
Digoxin - per clinical judgement
HydralazineIsordil - per clinical judgement
CoumadinAspirin - per clinical judgement
Beta Blockers - per clinical judgement
Calcium channel blockers - per clinical judgement
Non-cardiac meds - per clinical judgement
Spironolactone
1 already on - continue at current dose or dc as appropriate
2 already on - increase at dc if clinically indicated
3 not on - add at dc if clinically indicated
Other diuretic - discontinue and follow algorithm
Diet - 2 gm NaCl and 15 Liter total fluid restriction
Daily weights same scale
Accurate I and O
Oxygen - per clinical judgement
Diuretic therapy - Standardized Diuretic Algorithm based on initial creatinine clearance see below BNP must be started within 1-2 hours of randomization Diuretics will be started at 1 hour after start of the BNP infusion in BNP group Diuretics can be started immediately after randomization in the standard therapy group The study period is considered to start with initiation of BNP BNP group or diuretics Standard therapy group
Laboratory monitoring
Standard clinical care which includes daily electrolyte panel creatinine blood urea nitrogen sodium potassium Humoral function BNP ANP PRA Aldosterone ET N-proBNP Angiotensin II cGMP at baseline and prior to end of Natrecor infusion research labs Twenty ml of blood in standard EDTA tube and five ml of blood in EDTA tube with ACE inhibitor will be needed per blood draw
Vitals monitoring
Standard clinical care which includes established nursing protocols for use of BNP infusion on telemetry Introduction of BNP into clinical practice was piloted in the CCU and then on the cardiology telemetry units 4 Domatilla and 4 Joesph by the CHF group and is now standard clinical practice on these floors
Diuretic Algorithm
Initial dosing and subsequent dosing of diuretics are to follow the diuretic algorithm outlined below Can substitute bumex 1 mg bumex 40 mg furosemide Can delay progression to next level if within 10 of goal fluid balanceweight Clinician may use fluid balance OR weight to make decisions regarding progression to next level
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| A005 | None | None | None |