Adaptive Servo-Ventilation In Acute Heart Failure Patients Protecting the Heart and Kidneys

Heart Failure Clinical Trial

— ASLEEP PK  

Official title:

Adaptive Servo-Ventilation In Acute Heart Failure Patients Protecting the Heart

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02796638
• Other study ID #: H150082
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 2015
• Est. completion date: April 2021

Study information

• Verified date: January 2020
• Source: Veterans Medical Research Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary hypothesis of this study is: the use of minute ventilation-adaptive servo-ventilation (MV-ASV) during hospitalization will mitigate deterioration in renal function and prevent kidney injury in patients admitted with acute heart failure (AHF) compared to those receiving usual care. We will validate and extend our pilot study by taking a deeper dive into the effects of ASV on diuretic dose, urine output and new and exciting biomarkers of renal function and kidney injury. If our hypothesis proves correct, it strongly suggests that ASV lessens injury to the kidney and could lead to a new paradigm for the treatment of AHF. When use of high dose of diuretics are anticipated or in whom chronic kidney disease (CKD) or acute kidney injury (AKI) is present on arrival to the Emergency Department, use of MV-ASV might decrease the amount of diuretics needed, allow for continued use of ACE inhibitors, and ultimately mitigate rises in creatinine and decreases in effective glomerular filtration. Since kidney injury is a major factor in those patients with early 30-day readmission following discharge, this therapy could become quite popular.

Description:

OBJECTIVE(S): The main goal of this study is to evaluate the utility of a Minute Ventilation Adaptive Servo-ventilation (MV-ASV) device in mitigating deterioration in renal function and prevent kidney injury in patients admitted with acute heart failure compared to those receiving usual care. We will be assessing the effects of MV-ASV on diuretic dose, urine output and new and exciting biomarkers of renal function and kidney injury. If our hypothesis proves correct, it strongly suggests that ASV lessens hypoxia to the kidney and could lead to a new paradigm for the treatment of AHF. When use of high dose of diuretics are anticipated or in whom CKD or AKI is present on arrival to the Emergency Department, use of MV-ASV might decrease the amount of diuretics needed, allow for continued use of ACE inhibitors, and ultimately mitigate rises in creatinine and decreases in effective glomerular filtration. Since kidney injury is a major factor in those patients with early 30-day readmission following discharge, this therapy could become quite popular.

RESEARCH DESIGN: This is an interventional, principal investigator-initiated project with patient enrollment, cohort development and data analysis. We will recruit 66 patients with acute heart failure and evidence of volume overload and elevated BNP, since we anticipate a 10% dropout. Half will be pre-selected to have CKD with eGFR < 60 ml/min/1.73 m2. Randomization will be attempted within first six hours of hospital presentation. The participants will be randomized one of the following two groups: 1) those receiving only standard therapy or 2) those receiving standard therapy and adaptive servo-ventilation (ASV) therapy.

METHODOLOGY:

Methods:

1. Consenting of patient: every attempt will be made to consent within six hours of evaluation, as we feel there is a good window for ASV here. Maximum time to consent is 24 hours.

2. Sleep and breathing assessment: Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, Pulmonary Sleep Lab Questionnaire, Sleep Diary, Likert Scale

3. Blood Sample Collections:

4. Two 10cc (20cc total) blood samples in standard collection tubes will be obtained via venipuncture or a peripheral IV line from each enrolled patient at the time of enrollment.

5. One sample will be collected in a lithium heparin tube and the other sample will be collected in an EDTA tube. Initial blood samples will be collected after the initiation of standard medical therapy and stabilization for acute heart failure.

6. The blood samples will be analyzed for cardiac biomarkers such as BNP, high sensitivity troponins (hsTnI), endothelin-1 (ET-1), kidney injury molecule-1 (KIM-1) by Singulex, and adrenomedullin (hADM) by Sphingotec.

Remaining blood samples will be banked for future biomarker analysis. All samples will be held at the VASDHS in a clinical laboratory storage facility indefinitely for future analysis of biomarkers such as those of inflammation, fibrosis and cardiorenal syndrome. NO GENETIC TESTING will be done on the samples.

7. As obligated, we will report any incidental findings of FDA approved biomarkers performed, as a part of further analysis of banked specimens, to the patient through their treating physicians.

8. All specimens will be frozen at -80 degrees Celsius for storage.

9. Specimens with evidence of hemolysis will not be analyzed.

10. MV-ASV Treatment and Respiration Monitoring:

• Adaptive Servo-Ventilation (ASV) therapy will be placed on the patient by the respiratory therapy team as soon as the patient is enrolled in the study. The ASV device will be on ASV Auto mode, which has an automatic expiratory positive airway pressure (EPAP) adjustment based on the patient's breathing. The ASV Auto default EPAP range is 4-15cmH2O with a pressure support range of 3-15cmH2O. The backup rate of the ASV is adaptive based on the patient's respiratory rate. However, if the automatic ventilation setting is not suitable to maintain target ventilation, then a setting of 15 breaths per minute will be used.

• We will ask the patients to use the ASV therapy during all hours of sleeping during their stay in the hospital and during times when they are awake, if they feel comfortable using it.

• The patient will be closely monitored during the first few hours to make sure the patients are comfortable, have the right settings and are without mask leaks. The monitoring team will consist of members from Cardiology, Pulmonary Critical Care and Respiratory Therapy.

11. Repeat following assessments in the hospital each day for up to five days

• Two tubes of 10cc each (20 cc total)

• Likert dyspnea assessment

• Sleep diary entry once each day for up to 5 days

• Urine outputs

• Daily weights

• Dose of diuretics

12. Additional hospital data to be recorded:

• Presence of arrhythmias

• Need for inotropes

• Need for intubation

• Number of ICU days

• Total number of hospital days

• Need for renal consult

• Electrolytes

• BNP

• Troponins

13. Once the subject is discharged from the hospital, the following will happen:

• They will be seen at 30 days for following:

• Evaluation for events

• Sleepiness scales: Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, Pulmonary Sleep Lab Questionnaire, Sleep Diary, Likert Scale

• Two tubes of blood (10cc each) will be drawn, as described above to assess renal function and AKI

• They will not be reimbursed for this visit

14. Power analysis • The comparison of groups of size 30 and 30 has a power of 0.815 to detect an effect equal to a group difference of (0.75) standard deviations. This would apply to all variables in univariate tests at significance level of 0.05 with appropriate corrections for multiple comparisons.

CLINICAL RELATIONSHIPS: The potential benefit of this study includes the validation of the use of an ASV device in the treatment of heart failure. ASV treatment might decrease the amount of diuretics needed, allow for continued use of ACE inhibitors, and ultimately mitigate rises in creatinine and decreases in effective glomerular filtration. ASV treatment may lessen hypoxia to the kidney and could lead to a new paradigm for the treatment of AHF.

IMPACT/SIGNIFICANCE: Heart failure is a major cause of both death and healthcare spending in the United States. ASV is a cost effective, non-invasive treatment that can improve symptoms and cardiac outcomes in patients with heart failure. Validation of an MV-ASV device as an effective treatment could help improve prognosis and quality of life in patients with this often terminal condition.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: April 2021
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18 years and older.

2. Admitted with a clinical diagnosis of acute heart failure.

3. Evidence of congestion (rales, JVP, CXR, edema).

4. BNP >300pg/mL

5. If BMI >35 kg/m2, then BNP >100 pg/ml.

6. Consent within 24 hours of admission, but every attempt will be made to consent within six hours.

7. Patients with known sleep disordered breathing (SDB) can be included.

8. One-half of patients in each group will have chronic kidney disease (CKD) with GFR less than 60.

Exclusion Criteria:

1. Age < 18 years.

2. Unable to provide informed consent within 24 hours of admission.

3. Current participation in a pharmaceutical or treatment-related clinical study.

4. Intubated.

5. Hypercarbic (ie. Acute Respiratory Acidosis) from reasons other than acute heart failure.

6. Cardiogenic shock.

7. Clinical diagnosis of COPD exacerbation as the primary reason for hospital admission.

8. History of non-compliance to medications and treatment.

9. Pregnant women.

Related Conditions & MeSH terms

• Heart Failure
• Sleep Apnea, Obstructive

Intervention

Device:
• Adaptive Servo-Ventilation
A positive pressure airway device that increases and decreases inspiration pressure in concordance with the patient's natural breathing cycles.

Locations

Country	Name	City	State
United States	VA San Diego Healthcare System	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Veterans Medical Research Foundation	ResMed Foundation

Country where clinical trial is conducted

United States, 

References & Publications (4)

McCullough PA, Bouchard J, Waikar SS, Siew ED, Endre ZH, Goldstein SL, Koyner JL, Macedo E, Doi K, Di Somma S, Lewington A, Thadhani R, Chakravarthi R, Ice C, Okusa MD, Duranteau J, Doran P, Yang L, Jaber BL, Meehan S, Kellum JA, Haase M, Murray PT, Cruz — View Citation

Ng LL, Sandhu JK, Narayan H, Quinn PA, Squire IB, Davies JE, Bergmann A, Maisel A, Jones DJ. Proenkephalin and prognosis after acute myocardial infarction. J Am Coll Cardiol. 2014 Jan 28;63(3):280-9. doi: 10.1016/j.jacc.2013.09.037. Epub 2013 Oct 16. — View Citation

Ronco C, Cicoira M, McCullough PA. Cardiorenal syndrome type 1: pathophysiological crosstalk leading to combined heart and kidney dysfunction in the setting of acutely decompensated heart failure. J Am Coll Cardiol. 2012 Sep 18;60(12):1031-42. doi: 10.101 — View Citation

Ronco C, McCullough PA, Anker SD, Anand I, Aspromonte N, Bagshaw SM, Bellomo R, Berl T, Bobek I, Cruz DN, Daliento L, Davenport A, Haapio M, Hillege H, House A, Katz NM, Maisel A, Mankad S, Zanco P, Mebazaa A, Palazzuoli A, Ronco F, Shaw A, Sheinfeld G, S — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Renal Biomarkers	Mean paired change in measured blood urea nitrogen (BUN), serum creatinine (> 0.3 mg/dL increase in 48 hours), neutrophil gelatinase-associated lipocalin (NGAL), Pro-encephalin (Penkid), and endothelin	30 days post-discharge
Secondary	Change in Renal Biomarkers	Mean paired change in measured blood urea nitrogen (BUN), serum creatinine (> 0.3 mg/dL increase in 48 hours), neutrophil gelatinase-associated lipocalin (NGAL), Pro-encephalin (Penkid), and endothelin	up to 90 days post-discharge
Secondary	Reduction in Decrease of eGFR	A hypothesized reduction in eGFR decrease of 25% in the treatment group compared to the control group	up to 30 days post-discharge
Secondary	Reduction in Decrease of eGFR	A hypothesized reduction in eGFR decrease of 25% in the treatment group compared to the control group	up to 90 days post-discharge
Secondary	Disposition and post-discharge composite events	To assess patients for composite 30 days events, reduction of subendocardial ischemia in the hospital and at 30 days, reduction of LV wall stress and volume in the hospital and at 30 days; to assess patients for endothelial function, inflammation, and propensity toward fibrosis in the hospital and at 30 days, all of which can influence renal function.	up to 30 days post-discharge
Secondary	Disposition and post-discharge composite events	To assess patients for composite 30 days events, reduction of subendocardial ischemia in the hospital and at 90 days, reduction of LV wall stress and volume in the hospital and at 90 days; to assess patients for endothelial function, inflammation, and propensity toward fibrosis in the hospital and at 30 days, all of which can influence renal function	up to 90 days post-discharge
Secondary	Other markers of renal function	To assess patients for cumulative dose of loop diuretic, urine output, blood urea nitrogen, incidence of acute kidney injury (AKI), biomarkers of AKI, eGFR at 30 days, mean paired change in urinary biomarker levels, and serum creatinine.	up to 30 days post-discharge
Secondary	Other markers of renal function	To assess patients for cumulative dose of loop diuretic, urine output, blood urea nitrogen, incidence of acute kidney injury (AKI), biomarkers of AKI, eGFR at 30 days, mean paired change in urinary biomarker levels, and serum creatinine.	up to 90 days post-discharge