Heart FailureNCT04572867
Aquapheresis Efficacy in Outpatients With Decompensated Heart Failure
A study testing Aquapheresis and IV Diuretics in people with Heart Failure and Congestive Heart Failure, run by Ramona Gelzer Bell.
Trial summary
With this research the Investigators hope to learn if early aquapheresis in an outpatient setting will improve congestive heart failure symptoms in outpatients with decompensated heart failure who have been refractory to high dose diuretics. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Heart Failure, Congestive Heart Failure, Decompensated Heart Failure
- What is being tested?
- Aquapheresis and IV Diuretics
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 8 Jun 2021to 27 Jul 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects must be 18 years of age or older already on standard of care therapy including Angiotensin Converting Enzyme Inhibitors (ACE-I), Angiotensin
- Receptor Blockers (ARBs), Sacubitril/Valsartan, beta-blocker, oral diuretic (80 mg Lasix/2 mg Bumex/40 mg Torsemide+/-Thiazide diuretic), and meet the following inclusion criteria to be enrolled:
- CHF refractory to oral diuretic (80mg Lasix, 2mg Bumex, or 40mg Torsemide)
- Volume overload secondary to systolic or diastolic HF, evidenced by at least 2 of the following:
- Elevated BNP (>100)
- Paroxysmal nocturnal dyspnea or orthopnea
Show all 9Show fewer
- Elevated jugular venous distention (>/ 7 cm)
- X-ray findings consisted with CHF
- Presence of ascites or LE edema . -
Who cannot join
- Acute Coronary Syndrome
- Hypertensive urgency or emergency
- Rapid atrial fibrillation difficult to control
- Contraindication to anticoagulation
- Pregnancy
- Requires hemodialysis (> CR > 3.0 mg/dl)
Show all 9Show fewer
- Symptomatic hypotension
- Poor venous access
- Pressor dependent. -
About this study
Official title: Efficacy of Aquapheresis in Patients Treated as Outpatients With Decompensated Heart Failure at a Veterans Hospital
With this research the Investigators hope to learn if early aquapheresis in an outpatient setting will improve congestive heart failure symptoms in outpatients with decompensated heart failure who have been refractory to high dose diuretics. In previous trials in inpatient settings, aquapheresis has been demonstrated to improve quality of life and reduce hospital visits for those who have undergone the treatment. This study is one of the first to evaluate the effectiveness of aquapheresis in veterans with congestive heart failure in an outpatient setting.
The aquapheresis device, Aquadex FlexFlow® System, manufactured by CHF Solutions™, Minneapolis, MN, has been approved by the Food and Drug Administration (FDA) for removing excess sodium and fluid from patients suffering from volume overload, like in congestive heart failure.
Read the detailed description
Congestive heart failure (CHF) affects nearly 2% of the U.S. population, with almost 1 million hospital admissions for acute decompensated CHF annually. Congestive heart failure is the most frequent cause of hospitalization in patients over the age of 65. Patients admitted for acute decompensated heart failure (ADHF) have a high 6-month readmission rate for acute CHF, ranging from 23% to 40% in different studies. It is estimated that 25 to 30% of these patients are diuretic resistant with 50% of patients losing less than 5 lbs. from admission weight and 20% actually gaining weight during the hospitalization.
Although loop diuretics have not been shown to improve survival in patients with CHF, they effectively alleviate symptoms of congestion. Diuretics have been part of standard CHF therapy in all recent survival trials of β-blockers, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers. Loop diuretics have been shown to be the most effective diuretics as single agents in moderate to severe heart failure. However, loop diuretics may be associated with increased morbidity and mortality attributable to deleterious effects on neurohormonal activation, electrolyte balance, and cardiac and renal function.
Removal of excessive fluid in patients with CHF is usually achieved by a combination of fluid and salt restriction and loop diuretics, but in some cases volume overload persists. Diuretic resistance is common, especially after chronic exposure to loop diuretics; patients require escalating doses (PO or IV to bypass delayed absorption in gut due to bowel edema), addition of another diuretic that works on different part of renal tubules (i.e. Thiazides) +/- diuretic drip and, if still refractory, ultimately Aquapheresis (a form of ultrafiltration).
Aquapheresis (AQ) compared to IV diuretics in the UNLOAD Trial (10), AQ safely produced greater weight loss, fluid removal, and reduction in 90-day readmission rate compared to IV diuretic. A meta-analysis of 10 randomized control trials (RCTs) showed AQ not only to be effective but safe. These observations suggest that a strategy of early ultrafiltration may improve responsiveness to diuretics, quicker weight loss, decrease hospitalization, readmission to hospital, ER or doctor visits with minimal risks. As result of these trials, American Hospital Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of American (HFSA) guidelines state it is reasonable to start Aquapheresis in patients with obvious volume overload or patients who are refractory to high dose diuretics (IIa, LOE B). Moreover, while this therapy is part of standard of care in an inpatient setting, many hospitals as a result of Affordable Care Act (ACA), have taken to AQ on an outpatient setting to further decrease the burden and attended cost associated with management of CHF. But the Investigators are unaware of any other prospective outpatient studies that have looked at the outcomes and cost effectiveness of aquapheresis.
- Being tested
- Aquapheresis, IV Diuretics
- Keywords
- Aquapheresis, Diuresis
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AquapheresisDevice
Also called Ultrafiltration, Hemodialysis
The Aquadex FlexFlow® Fluid Removal System (from CHF Solutions™, Minneapolis, MN) is an FDA approved device that provides mechanical isosmotic fluid removal in volume-overloaded CHF patients via veno-venous ultrafiltration, and has been used in patients with congestive heart failure refractory to diuretics, it should be considered standard of care also. This study is using it in a randomized, controlled study in the Outpatient setting. The Aquadex FlexFlow® Fluid Removal System is a dual rotary pump device used with a sterile, single-use UF 500 Blood Circuit Set. Blood withdrawal is usually from a peripheral arm vein (such as the antecubital vein), using a 16 or 18- gauge, 3.5 cm catheter (similar to a standard IV catheter). A similar IV catheter is used for blood return via a second peripheral vein (typically in the forearm).
IV DiureticsDrug
Also called Intravenous Diuretics
Active Comparator: Intravenous Diuretics Per protocol (Fig 2), if randomized to IV diuretic therapy arm (IV), the patient will receive initial dose of IV diuretic based on base line renal function; then the dose will be doubled every 2 hrs if refractory, to a maximum of 8mg IV Bumex (or 320mg IV Lasix). Metolazone may be added at 2.5mg PO 30 minutes before loop diuretic if CR< 2.0, or 5mg PO if Cr > 2.0, if refractory to high dose loop diuretic. If the patient in IV arm is refractory to max 320 mg IV Lasix or 8 mg IV Bumex plus Metolazone then the patient may cross over to AQ arm.
| Study group | Role | What they receive |
|---|---|---|
| Aquapheresis | Experimental | Per protocol, if randomized to Aquapheresis arm (AQ), all diuretics are discontinued and AQ will be administered as per established protocol. BMP and CBC will be checked prior to initiation and as needed, 7-10 days, 30, 60 and 90 days post discharge. Note, aquapheresis rate is to be decreased by 100 cc/hr if Hgb increases by 1gm/dL, and stopped if rate is decreased to 50 cc/hr or reaches euvolemia, whichever comes first. Receives: Device: Aquapheresis |
| IV Diuretics | Active comparator | Per protocol (Fig 2), if randomized to IV diuretic therapy arm (IV), the patient will receive initial dose of IV diuretic based on base line renal function; then the dose will be doubled every 2 hrs if refractory, to a maximum of 8mg IV Bumex (or 320mg IV Lasix). Metolazone may be added at 2.5mg PO 30 minutes before loop diuretic if CR< 2.0, or 5mg PO if Cr > 2.0, if refractory to high dose loop diuretic. If a patient in IV arm is refractory to maximum 320 mg IV Lasix or 8 mg IV Bumex plus Metolazone then the patient may cross over to AQ arm. Receives: Drug: IV Diuretics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Hospitalizations by 7 days post-treatment
Compare number of hospitalization readmissions for CHF between Intervention (Aquaphersis arm) \& Control groups
Measured: Between outpatient treatment and 7-days after outpatient treatment
Number of Hospitalizations by 30 days post-treatment
Compare number of hospitalization readmissions for CHF between Intervention (Aquaphersis arm) \& Control groups
Measured: Between outpatient treatment and 30 days after outpatient treatment
Number of Hospitalizations by 60 days post-treatment
Compare number of hospitalization readmissions for CHF between Intervention (Aquaphersis arm) \& Control groups
Measured: Between outpatient treatment and 60 days after outpatient treatment
Number of Hospitalizations by 90 days post-treatment
Compare number of hospitalization readmissions for CHF between Intervention (Aquaphersis arm) \& Control groups
Measured: Between outpatient treatment and 90 days after outpatient treatment
Weight change by 7 days post-treatment
Compare weight change (pounds) in patients between Intervention \& Control groups
Measured: Outpatient treatment to 7 days after outpatient treatment
Weight change by 30 days post-treatment
Compare weight change (pounds) in patients between Intervention \& Control groups
Measured: Outpatient treatment to 30 days after outpatient treatment
Weight change by 60 days post-treatment
Compare weight change (pounds) in patients between Intervention \& Control groups
Measured: Outpatient treatment to 60 days after outpatient treatment
Weight change by 90 days post-treatment
Compare weight change (pounds) in patients between Intervention \& Control groups
Measured: Outpatient treatment to 90 days after outpatient treatment
Secondary outcomes (39)
Total fluid removal
Compare total fluid removal (ml) in patients between Intervention \& Control groups
Measured: Baseline (Randomization) to outpatient discharge
Blood urea nitrogen at Baseline
Compare Blood urea nitrogen (BUN; mg/dl) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: Baseline (Randomization)
Blood urea nitrogen at 7 days post-treatment
Compare Blood urea nitrogen (BUN; mg/dl) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 7 days after outpatient treatment
Blood urea nitrogen at 30 days post-treatment
Compare Blood urea nitrogen (BUN; mg/dl) (higher than normal range is worse)) in patients between Intervention \& Control groups
Measured: 30 days after outpatient treatment
Blood urea nitrogen at 60 days post-treatment
Compare Blood urea nitrogen (BUN; mg/dl) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 60 days after outpatient treatment
Blood urea nitrogen at 90 days post-treatment
Compare Blood urea nitrogen (BUN; mg/dl) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 90 days after outpatient treatment
Creatinine at Baseline
Compare Creatinine (Cr; mg/dl) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: Baseline (Randomization)
Creatinine at 7 days post-treatment
Compare Creatinine (Cr; mg/dl) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 7 days after outpatient treatment
Creatinine at 30 days post-treatment
Compare Creatinine (Cr; mg/dl) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 30 days after outpatient treatment
Creatinine at 60 days post-treatment
Compare Creatinine (Cr; mg/dl) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 60 days after outpatient treatment
Creatinine at 90 days post-treatment
Compare Creatinine (Cr; mg/dl) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 90 days after outpatient treatment
Glomerular filtration rate at Baseline
Compare Glomerular filtration rate (GFR; ml/min/1.73 meters squared) (lower than normal range is worse) in patients between Intervention \& Control groups
Measured: Baseline (Randomization)
Glomerular filtration rate at 7 days post-treatment
Compare Glomerular filtration rate (GFR; ml/min/1.73 meters squared) (lower than normal range is worse) in patients between Intervention \& Control groups
Measured: 7 days after outpatient treatment
Glomerular filtration rate at 30 days post-treatment
Compare Glomerular filtration rate (GFR; ml/min/1.73 meters squared) (lower than normal range is worse) in patients between Intervention \& Control groups
Measured: 30 days after outpatient treatment
Glomerular filtration rate at 60 days post-treatment
Compare Glomerular filtration rate (GFR; ml/min/1.73 meters squared) (lower than normal range is worse) in patients between Intervention \& Control groups
Measured: 60 days after outpatient treatment
Glomerular filtration rate at 90 days post-treatment
Compare Glomerular filtration rate (GFR; ml/min/1.73 meters squared) (lower than normal range is worse) in patients between Intervention \& Control groups
Measured: 90 days after outpatient treatment
Brain natriuretic peptide (BNP) test at Baseline
Compare BNP (pg/ml of blood) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: Baseline (Randomization)
Brain natriuretic peptide (BNP) test at 7 days post-treatment
Compare BNP (pg/ml of blood) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 7 days after outpatient treatment
Brain natriuretic peptide (BNP) test at 30 days post-treatment
Compare BNP (pg/ml of blood) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 30 days after outpatient treatment
Brain natriuretic peptide (BNP) test at 60 days post-treatment
Compare BNP (pg/ml of blood) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 60 days after outpatient treatment
Brain natriuretic peptide (BNP) test at 90 days post-treatment
Compare BNP (pg/ml of blood) (higher than normal range is worse) in patients between Intervention \& Control groups
Measured: 90 days after outpatient treatment
6-minute Walk Test at Baseline
Compare 6-minute Walk Test (meters/6 minutes; less distance means more disability) in patients between Intervention \& Control groups
Measured: Baseline (Randomization)
6-minute Walk Test at 7 days post-treatment
Compare 6-minute Walk Test (meters/6 minutes; less distance means more disability) in patients between Intervention \& Control groups
Measured: 7 days after outpatient treatment
6-minute Walk Test at 30 days post-treatment
Compare 6-minute Walk Test (meters/6 minutes; less distance means more disability) in patients between Intervention \& Control groups
Measured: 30 days after outpatient treatment
6-minute Walk Test at 60 days post-treatment
Compare 6-minute Walk Test (meters/6 minutes; less distance means more disability) in patients between Intervention \& Control groups
Measured: 60 days after outpatient treatment
6-minute Walk Test at 90 days post-treatment
Compare 6-minute Walk Test (meters/6 minutes; less distance means more disability) in patients between Intervention \& Control groups
Measured: 90 days after outpatient treatment
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Compare Minnesota Living with Heart Failure Questionnaire (MLWHFQ) (total score; higher score means more impairment) in patients between Intervention \& Control groups
Measured: Baseline (Randomization)
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Compare Minnesota Living with Heart Failure Questionnaire (MLWHFQ) (total score; higher score means more impairment) in patients between Intervention \& Control groups
Measured: 7 days after outpatient treatment
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Compare Minnesota Living with Heart Failure Questionnaire (MLWHFQ) (total score; higher score means more impairment) in patients between Intervention \& Control groups
Measured: 30 days after outpatient treatment
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Compare Minnesota Living with Heart Failure Questionnaire (MLWHFQ) (total score; higher score means more impairment) in patients between Intervention \& Control groups
Measured: 60 days after outpatient treatment
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Compare Minnesota Living with Heart Failure Questionnaire (MLWHFQ) (total score; higher score means more impairment) in patients between Intervention \& Control groups
Measured: 90 days after outpatient treatment
SF-36 at Baseline
Compare SF-36 weighted sums (0-100 scale; lower score means more disability) in patients between Intervention \& Control groups
Measured: Baseline (Randomization)
SF-36 at 7 days post-treatment
Compare SF-36 weighted sums (0-100 scale; lower score means more disability) in patients between Intervention \& Control groups
Measured: 7 days after outpatient treatment
SF-36 at 30 days post-treatment
Compare SF-36 weighted sums (0-100 scale; lower score means more disability) in patients between Intervention \& Control groups
Measured: 30 days after outpatient treatment
SF-36 at 60 days post-treatment
Compare SF-36 weighted sums (0-100 scale; lower score means more disability) in patients between Intervention \& Control groups
Measured: 60 days after outpatient treatment
SF-36 at 90 days post-treatment
Compare SF-36 weighted sums (0-100 scale; lower score means more disability) in patients between Intervention \& Control groups
Measured: 90 days after outpatient treatment
Adverse events: bleeding incidents during Outpatient treatment
Compare number of Adverse Events (bleeding incidents) in patients between Intervention \& Control groups: bleeding, line-related infection, etc.
Measured: Start of treatment to discharge, which is usually the same day, but up to 3 days post-treatment, if medically necessary.
Adverse events: line infections during Outpatient treatment
Compare number of Adverse Events (line infections) in patients between Intervention \& Control groups: bleeding, line-related infection, etc.
Measured: Start of treatment to up to 14 days post-treatment.
Costs
Compare costs (dollars) between Intervention \& Control groups
Measured: Baseline (Randomization) to 90 days post-discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2020
- Study start8 Jun 2021
- Primary completion27 Jul 2021
- Study completion27 Jul 2021
Why it stopped: Due to low enrollment, COVID-19 pandemic causing suspension of most outpatient elective procedures, and no protected research time, Dr. Gelzer Bell is unable to continue this study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a Controlled Trial with two arms (aquapheresis and IV diuretics/Control), but there is the potential for cross-over to aquapheresis if a patient receiving diuretics is refractory to maximum doses of IV diuretics.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ramona Gelzer Bell
- Sponsor type
- US federal agency
- Responsible party
- Sponsor-investigator, Ramona Gelzer Bell, James A. Haley Veterans Administration Hospital
- Investigators
- Ramona Gelzer Bell, MD, Principal investigator, James A. Haley Veterans Administration Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04572867
- Sponsor's protocol ID
- AQUA
- Status last verified
- Aug 2021
- First submitted
- 24 Aug 2020
- Last updated
- 30 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Polanczyk CA, Newton C, Dec GW, Di Salvo TG. Quality of care and hospital readmission in congestive heart failure: an explicit review process. J Card Fail. 2001 Dec;7(4):289-98. doi: 10.1054/jcaf.2001.28931.
PubMed 11782850Hamner JB, Ellison KJ. Predictors of hospital readmission after discharge in patients with congestive heart failure. Heart Lung. 2005 Jul-Aug;34(4):231-9. doi: 10.1016/j.hrtlng.2005.01.001.
PubMed 16027642Krumholz HM, Chen YT, Wang Y, Vaccarino V, Radford MJ, Horwitz RI. Predictors of readmission among elderly survivors of admission with heart failure. Am Heart J. 2000 Jan;139(1 Pt 1):72-7. doi: 10.1016/s0002-8703(00)90311-9.
PubMed 10618565Lee WY, Capra AM, Jensvold NG, Gurwitz JH, Go AS; Epidemiology, Practice, Outcomes, and Cost of Heart Failure (EPOCH) Study. Gender and risk of adverse outcomes in heart failure. Am J Cardiol. 2004 Nov 1;94(9):1147-52. doi: 10.1016/j.amjcard.2004.07.081.
PubMed 15518609Adams KF Jr, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, Berkowitz RL, Galvao M, Horton DP; ADHERE Scientific Advisory Committee and Investigators. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005 Feb;149(2):209-16. doi: 10.1016/j.ahj.2004.08.005.
PubMed 15846257Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Am J Cardiol. 1999 Jan 21;83(2A):1A-38A. No abstract available.
PubMed 10072251Wilcox CS. Diuretics. In: Brenner BM, Rector FC. The kidney. Philadelphia: WB Saunders, 1996: 2299-330.
Ellison DH. Diuretic therapy and resistance in congestive heart failure. Cardiology. 2001;96(3-4):132-43. doi: 10.1159/000047397.
PubMed 11805380Schrier RW. Role of diminished renal function in cardiovascular mortality: marker or pathogenetic factor? J Am Coll Cardiol. 2006 Jan 3;47(1):1-8. doi: 10.1016/j.jacc.2005.07.067. Epub 2005 Dec 15.
PubMed 16386657Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, Jaski BE, Fang JC, Feller ED, Haas GJ, Anderson AS, Schollmeyer MP, Sobotka PA; UNLOAD Trial Investigators. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol. 2007 Feb 13;49(6):675-83. doi: 10.1016/j.jacc.2006.07.073. Epub 2007 Jan 26.
PubMed 17291932Sharma A, Hermann DD, Mehta RL. Clinical benefit and approach of ultrafiltration in acute heart failure. Cardiology. 2001;96(3-4):144-54. doi: 10.1159/000047398.
PubMed 11805381Marenzi G, Lauri G, Grazi M, Assanelli E, Campodonico J, Agostoni P. Circulatory response to fluid overload removal by extracorporeal ultrafiltration in refractory congestive heart failure. J Am Coll Cardiol. 2001 Oct;38(4):963-8. doi: 10.1016/s0735-1097(01)01479-6.
PubMed 11583865Rimondini A, Cipolla CM, Della Bella P, Grazi S, Sisillo E, Susini G, Guazzi MD. Hemofiltration as short-term treatment for refractory congestive heart failure. Am J Med. 1987 Jul;83(1):43-8. doi: 10.1016/0002-9343(87)90495-5.
PubMed 3605181Jaski BE, Ha J, Denys BG, Lamba S, Trupp RJ, Abraham WT. Peripherally inserted veno-venous ultrafiltration for rapid treatment of volume overloaded patients. J Card Fail. 2003 Jun;9(3):227-31. doi: 10.1054/jcaf.2003.28.
PubMed 12815573Agostoni P, Marenzi G, Lauri G, Perego G, Schianni M, Sganzerla P, Guazzi MD. Sustained improvement in functional capacity after removal of body fluid with isolated ultrafiltration in chronic cardiac insufficiency: failure of furosemide to provide the same result. Am J Med. 1994 Mar;96(3):191-9. doi: 10.1016/0002-9343(94)90142-2.
PubMed 8154506
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Aquapheresis in Patients Treated as Outpatients With Decompensated Heart Failure at a Veterans Hospital
- ClinicalTrials.gov ID
- NCT04572867
- Acronym / sponsor ID
- AQUA
- Keywords
- Aquapheresis, Diuresis
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to low enrollment, COVID-19 pandemic causing suspension of most outpatient elective procedures, and no protected research time, Dr. Gelzer Bell is unable to continue this study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ramona Gelzer BellUS federal agency
- Study start
- 8 Jun 2021 (actual)
- Primary completion
- 27 Jul 2021 (actual)
- Study completion
- 27 Jul 2021 (actual)
- First posted
- 1 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With this research the Investigators hope to learn if early aquapheresis in an outpatient setting will improve congestive heart failure symptoms in outpatients with decompensated heart failure who have been refractory to high dose diuretics. In previous trials in inpatient settings, aquapheresis has been demonstrated to improve quality of life and reduce hospital visits for those who have undergone the treatment. This study is one of the first to evaluate the effectiveness of aquapheresis in veterans with congestive heart failure in an outpatient setting.
The aquapheresis device, Aquadex FlexFlow® System, manufactured by CHF Solutions™, Minneapolis, MN, has been approved by the Food and Drug Administration (FDA) for removing excess sodium and fluid from patients suffering from volume overload, like in congestive heart failure.
Detailed description
Congestive heart failure (CHF) affects nearly 2% of the U.S. population, with almost 1 million hospital admissions for acute decompensated CHF annually. Congestive heart failure is the most frequent cause of hospitalization in patients over the age of 65. Patients admitted for acute decompensated heart failure (ADHF) have a high 6-month readmission rate for acute CHF, ranging from 23% to 40% in different studies. It is estimated that 25 to 30% of these patients are diuretic resistant with 50% of patients losing less than 5 lbs. from admission weight and 20% actually gaining weight during the hospitalization.
Although loop diuretics have not been shown to improve survival in patients with CHF, they effectively alleviate symptoms of congestion. Diuretics have been part of standard CHF therapy in all recent survival trials of β-blockers, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers. Loop diuretics have been shown to be the most effective diuretics as single agents in moderate to severe heart failure. However, loop diuretics may be associated with increased morbidity and mortality attributable to deleterious effects on neurohormonal activation, electrolyte balance, and cardiac and renal function.
Removal of excessive fluid in patients with CHF is usually achieved by a combination of fluid and salt restriction and loop diuretics, but in some cases volume overload persists. Diuretic resistance is common, especially after chronic exposure to loop diuretics; patients require escalating doses (PO or IV to bypass delayed absorption in gut due to bowel edema), addition of another diuretic that works on different part of renal tubules (i.e. Thiazides) +/- diuretic drip and, if still refractory, ultimately Aquapheresis (a form of ultrafiltration).
Aquapheresis (AQ) compared to IV diuretics in the UNLOAD Trial (10), AQ safely produced greater weight loss, fluid removal, and reduction in 90-day readmission rate compared to IV diuretic. A meta-analysis of 10 randomized control trials (RCTs) showed AQ not only to be effective but safe. These observations suggest that a strategy of early ultrafiltration may improve responsiveness to diuretics, quicker weight loss, decrease hospitalization, readmission to hospital, ER or doctor visits with minimal risks. As result of these trials, American Hospital Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of American (HFSA) guidelines state it is reasonable to start Aquapheresis in patients with obvious volume overload or patients who are refractory to high dose diuretics (IIa, LOE B). Moreover, while this therapy is part of standard of care in an inpatient setting, many hospitals as a result of Affordable Care Act (ACA), have taken to AQ on an outpatient setting to further decrease the burden and attended cost associated with management of CHF. But the Investigators are unaware of any other prospective outpatient studies that have looked at the outcomes and cost effectiveness of aquapheresis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a Controlled Trial with two arms (aquapheresis and IV diuretics/Control), but there is the potential for cross-over to aquapheresis if a patient receiving diuretics is refractory to maximum doses of IV diuretics.
| Arm | Type | Receives |
|---|---|---|
| Aquapheresis | Experimental | Device: AquapheresisPer protocol, if randomized to Aquapheresis arm (AQ), all diuretics are discontinued and AQ will be administered as per established protocol. BMP and CBC will be checked prior to initiation and as needed, 7-10 days, 30, 60 and 90 days post discharge. Note, aquapheresis rate is to be decreased by 100 cc/hr if Hgb increases by 1gm/dL, and stopped if rate is decreased to 50 cc/hr or reaches euvolemia, whichever comes first. |
| IV Diuretics | Active comparator | Drug: IV DiureticsPer protocol (Fig 2), if randomized to IV diuretic therapy arm (IV), the patient will receive initial dose of IV diuretic based on base line renal function; then the dose will be doubled every 2 hrs if refractory, to a maximum of 8mg IV Bumex (or 320mg IV Lasix). Metolazone may be added at 2.5mg PO 30 minutes before loop diuretic if CR< 2.0, or 5mg PO if Cr > 2.0, if refractory to high dose loop diuretic. If a patient in IV arm is refractory to maximum 320 mg IV Lasix or 8 mg IV Bumex plus Metolazone then the patient may cross over to AQ arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects must be 18 years of age or older already on standard of care therapy including Angiotensin Converting Enzyme Inhibitors (ACE-I), Angiotensin
- Receptor Blockers (ARBs), Sacubitril/Valsartan, beta-blocker, oral diuretic (80 mg Lasix/2 mg Bumex/40 mg Torsemide+/-Thiazide diuretic), and meet the following inclusion criteria to be enrolled:
- CHF refractory to oral diuretic (80mg Lasix, 2mg Bumex, or 40mg Torsemide)
- Volume overload secondary to systolic or diastolic HF, evidenced by at least 2 of the following:
Key exclusion criteria (9 listed)
- Acute Coronary Syndrome
- Hypertensive urgency or emergency
- Rapid atrial fibrillation difficult to control
- Contraindication to anticoagulation
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AquapheresisAlso: Ultrafiltration, HemodialysisThe Aquadex FlexFlow® Fluid Removal System (from CHF Solutions™, Minneapolis, MN) is an FDA approved device that provides mechanical isosmotic fluid removal in volume-overloaded CHF patients via veno-venous ultrafiltration, and has been used in patients with congestive heart failure refractory to diuretics, it should be considered standard of care also. This study is using it in a randomized, controlled study in the Outpatient setting. The Aquadex FlexFlow® Fluid Removal System is a dual rotary pump device used with a sterile, single-use UF 500 Blood Circuit Set. Blood withdrawal is usually from a peripheral arm vein (such as the antecubital vein), using a 16 or 18- gauge, 3.5 cm catheter (similar to a standard IV catheter). A similar IV catheter is used for blood return via a second peripheral vein (typically in the forearm). | Device | Aquapheresis |
| IV DiureticsAlso: Intravenous DiureticsActive Comparator: Intravenous Diuretics Per protocol (Fig 2), if randomized to IV diuretic therapy arm (IV), the patient will receive initial dose of IV diuretic based on base line renal function; then the dose will be doubled every 2 hrs if refractory, to a maximum of 8mg IV Bumex (or 320mg IV Lasix). Metolazone may be added at 2.5mg PO 30 minutes before loop diuretic if CR< 2.0, or 5mg PO if Cr > 2.0, if refractory to high dose loop diuretic. If the patient in IV arm is refractory to max 320 mg IV Lasix or 8 mg IV Bumex plus Metolazone then the patient may cross over to AQ arm. | Drug | IV Diuretics |
Primary outcome
Number of Hospitalizations by 7 days post-treatment
Time frame: Between outpatient treatment and 7-days after outpatient treatment
Compare number of hospitalization readmissions for CHF between Intervention (Aquaphersis arm) \& Control groups
Number of Hospitalizations by 30 days post-treatment
Time frame: Between outpatient treatment and 30 days after outpatient treatment
Compare number of hospitalization readmissions for CHF between Intervention (Aquaphersis arm) \& Control groups
Number of Hospitalizations by 60 days post-treatment
Time frame: Between outpatient treatment and 60 days after outpatient treatment
Compare number of hospitalization readmissions for CHF between Intervention (Aquaphersis arm) \& Control groups
Number of Hospitalizations by 90 days post-treatment
Time frame: Between outpatient treatment and 90 days after outpatient treatment
Compare number of hospitalization readmissions for CHF between Intervention (Aquaphersis arm) \& Control groups
Weight change by 7 days post-treatment
Time frame: Outpatient treatment to 7 days after outpatient treatment
Compare weight change (pounds) in patients between Intervention \& Control groups
Weight change by 30 days post-treatment
Time frame: Outpatient treatment to 30 days after outpatient treatment
Compare weight change (pounds) in patients between Intervention \& Control groups
Weight change by 60 days post-treatment
Time frame: Outpatient treatment to 60 days after outpatient treatment
Compare weight change (pounds) in patients between Intervention \& Control groups
Weight change by 90 days post-treatment
Time frame: Outpatient treatment to 90 days after outpatient treatment
Compare weight change (pounds) in patients between Intervention \& Control groups
39 secondary outcomes
Total fluid removal
Time frame: Baseline (Randomization) to outpatient discharge
Blood urea nitrogen at Baseline
Time frame: Baseline (Randomization)
Blood urea nitrogen at 7 days post-treatment
Time frame: 7 days after outpatient treatment
Blood urea nitrogen at 30 days post-treatment
Time frame: 30 days after outpatient treatment
Blood urea nitrogen at 60 days post-treatment
Time frame: 60 days after outpatient treatment
Blood urea nitrogen at 90 days post-treatment
Time frame: 90 days after outpatient treatment
Creatinine at Baseline
Time frame: Baseline (Randomization)
Creatinine at 7 days post-treatment
Time frame: 7 days after outpatient treatment
Creatinine at 30 days post-treatment
Time frame: 30 days after outpatient treatment
Creatinine at 60 days post-treatment
Time frame: 60 days after outpatient treatment
Creatinine at 90 days post-treatment
Time frame: 90 days after outpatient treatment
Glomerular filtration rate at Baseline
Time frame: Baseline (Randomization)
Glomerular filtration rate at 7 days post-treatment
Time frame: 7 days after outpatient treatment
Glomerular filtration rate at 30 days post-treatment
Time frame: 30 days after outpatient treatment
Glomerular filtration rate at 60 days post-treatment
Time frame: 60 days after outpatient treatment
Glomerular filtration rate at 90 days post-treatment
Time frame: 90 days after outpatient treatment
Brain natriuretic peptide (BNP) test at Baseline
Time frame: Baseline (Randomization)
Brain natriuretic peptide (BNP) test at 7 days post-treatment
Time frame: 7 days after outpatient treatment
Brain natriuretic peptide (BNP) test at 30 days post-treatment
Time frame: 30 days after outpatient treatment
Brain natriuretic peptide (BNP) test at 60 days post-treatment
Time frame: 60 days after outpatient treatment
Brain natriuretic peptide (BNP) test at 90 days post-treatment
Time frame: 90 days after outpatient treatment
6-minute Walk Test at Baseline
Time frame: Baseline (Randomization)
6-minute Walk Test at 7 days post-treatment
Time frame: 7 days after outpatient treatment
6-minute Walk Test at 30 days post-treatment
Time frame: 30 days after outpatient treatment
6-minute Walk Test at 60 days post-treatment
Time frame: 60 days after outpatient treatment
6-minute Walk Test at 90 days post-treatment
Time frame: 90 days after outpatient treatment
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Time frame: Baseline (Randomization)
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Time frame: 7 days after outpatient treatment
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Time frame: 30 days after outpatient treatment
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Time frame: 60 days after outpatient treatment
Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
Time frame: 90 days after outpatient treatment
SF-36 at Baseline
Time frame: Baseline (Randomization)
SF-36 at 7 days post-treatment
Time frame: 7 days after outpatient treatment
SF-36 at 30 days post-treatment
Time frame: 30 days after outpatient treatment
SF-36 at 60 days post-treatment
Time frame: 60 days after outpatient treatment
SF-36 at 90 days post-treatment
Time frame: 90 days after outpatient treatment
Adverse events: bleeding incidents during Outpatient treatment
Time frame: Start of treatment to discharge, which is usually the same day, but up to 3 days post-treatment, if medically necessary.
Adverse events: line infections during Outpatient treatment
Time frame: Start of treatment to up to 14 days post-treatment.
Costs
Time frame: Baseline (Randomization) to 90 days post-discharge
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2021.
- Background: PubMed 11782850Polanczyk CA, Newton C, Dec GW, Di Salvo TG. Quality of care and hospital readmission in congestive heart failure: an explicit review process. J Card Fail. 2001 Dec;7(4):289-98. doi: 10.1054/jcaf.2001.28931.
- Background: PubMed 16027642Hamner JB, Ellison KJ. Predictors of hospital readmission after discharge in patients with congestive heart failure. Heart Lung. 2005 Jul-Aug;34(4):231-9. doi: 10.1016/j.hrtlng.2005.01.001.
- Background: PubMed 10618565Krumholz HM, Chen YT, Wang Y, Vaccarino V, Radford MJ, Horwitz RI. Predictors of readmission among elderly survivors of admission with heart failure. Am Heart J. 2000 Jan;139(1 Pt 1):72-7. doi: 10.1016/s0002-8703(00)90311-9.
- Background: PubMed 15518609Lee WY, Capra AM, Jensvold NG, Gurwitz JH, Go AS; Epidemiology, Practice, Outcomes, and Cost of Heart Failure (EPOCH) Study. Gender and risk of adverse outcomes in heart failure. Am J Cardiol. 2004 Nov 1;94(9):1147-52. doi: 10.1016/j.amjcard.2004.07.081.
- Background: PubMed 15846257Adams KF Jr, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, Berkowitz RL, Galvao M, Horton DP; ADHERE Scientific Advisory Committee and Investigators. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005 Feb;149(2):209-16. doi: 10.1016/j.ahj.2004.08.005.
- Background: PubMed 10072251Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Am J Cardiol. 1999 Jan 21;83(2A):1A-38A. No abstract available.
- BackgroundWilcox CS. Diuretics. In: Brenner BM, Rector FC. The kidney. Philadelphia: WB Saunders, 1996: 2299-330.
- Background: PubMed 11805380Ellison DH. Diuretic therapy and resistance in congestive heart failure. Cardiology. 2001;96(3-4):132-43. doi: 10.1159/000047397.
- Background: PubMed 16386657Schrier RW. Role of diminished renal function in cardiovascular mortality: marker or pathogenetic factor? J Am Coll Cardiol. 2006 Jan 3;47(1):1-8. doi: 10.1016/j.jacc.2005.07.067. Epub 2005 Dec 15.
- Background: PubMed 17291932Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, Jaski BE, Fang JC, Feller ED, Haas GJ, Anderson AS, Schollmeyer MP, Sobotka PA; UNLOAD Trial Investigators. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol. 2007 Feb 13;49(6):675-83. doi: 10.1016/j.jacc.2006.07.073. Epub 2007 Jan 26.
- Background: PubMed 11805381Sharma A, Hermann DD, Mehta RL. Clinical benefit and approach of ultrafiltration in acute heart failure. Cardiology. 2001;96(3-4):144-54. doi: 10.1159/000047398.
- Background: PubMed 11583865Marenzi G, Lauri G, Grazi M, Assanelli E, Campodonico J, Agostoni P. Circulatory response to fluid overload removal by extracorporeal ultrafiltration in refractory congestive heart failure. J Am Coll Cardiol. 2001 Oct;38(4):963-8. doi: 10.1016/s0735-1097(01)01479-6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramona Gelzer Bell, MD principal investigator
James A. Haley Veterans Administration Hospital
Questions about this trial
What is this clinical trial studying?
A study testing Aquapheresis and IV Diuretics in people with Heart Failure and Congestive Heart Failure, run by Ramona Gelzer Bell.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Hospitalizations by 7 days post-treatment (time frame: Between outpatient treatment and 7-days after outpatient treatment). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04572867, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2021.