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Heart FailurePhase 3CARRESSNCT00608491

Effectiveness of Ultrafiltration in Treating People With Acute Decompensated Heart Failure and Cardiorenal Syndrome (The CARRESS Study)

A Phase 3 study testing Stepped pharmacologic care and Ultrafiltration in people with Heart Failure, run by Duke University at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Heart failure is a serious condition in which the heart's ability to pump blood through the body is impaired, often making a person feel weak or fatigued. When a person's condition worsens to the point of hospitalization, that person is said to have acute decompensated heart failure (ADHF). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Heart Failure
What is being tested?
Stepped pharmacologic care and Ultrafiltration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
188 participants
Where
9 sitesin 2 countries
Study dates
Mar 2008to Jun 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • age 18 or older
  • admitted to the hospital with a primary diagnosis of decompensated heart failure
  • onset of cardiorenal syndrome after hospitalization or pre-hospitalization
  • after hospitalization - onset of cardiorenal syndrome after hospitalization must occur within 10 days from the time of admission after receiving IV diuretics
  • pre-hospitalization - onset of cardiorenal syndrome pre-hospitalization must occur within 12 weeks of the index hospitalization in the setting of escalating doses of outpatient diuretics
  • persistent volume overload

Who cannot join

  • intravascular volume depletion based on investigator"s clinical assessment
  • acute coronary syndrome within 4 weeks
  • indication for hemodialysis
  • creatinine > 3.5 mg per deciliter at admission to the hospital
  • systolic blood pressure < 90 mmHg at the time of enrollment
  • alternative explanation for worsening renal function such as obstructive nephropathy,contrast induced nephropathy, acute tubular necrosis
Show all 18Show fewer
  • Hematocrit > 45%
  • poor venous access
  • clinical instability likely to require the addition of intravenous vasoactive drugs including vasodilators and/or inotropic agents
  • allergy or contraindications to the use of heparin
  • the use of iodinated radio contrast material in the last 72 hours or anticipated use of IV contrast during the current hospitalization
  • known bilateral renal artery stenosis
  • active myocarditis
  • hypertrophic obstructive cardiomyopathy
  • severe valvular stenosis
  • complex congenital heart disease
  • sepsis or ongoing systemic infection
  • enrollment in another clinical trial involving medical or device based interventions

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States8 sites

  • Morehouse School of Medicine

    Atlanta, Georgia, 30310

  • University of Vermont - Fletcher Allen Health Care

    Burlington, Vermont, 05401

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Minnesota Heart Failure Network

    Minneapolis, Minnesota, 55415

  • University of Utah Health Sciences Center

    Murray, Utah, 84107

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

Canada1 site

  • Montreal Heart Institute

    Montreal, Quebec, H1T - 1C8

Other trials in Canada

About this study

Official title: CARdiorenal REScue Study in Acute Decompensated Heart Failure: CARRESS

Heart failure is a serious condition in which the heart's ability to pump blood through the body is impaired, often making a person feel weak or fatigued. When a person's condition worsens to the point of hospitalization, that person is said to have acute decompensated heart failure (ADHF). Abnormal kidney function in association with cardiac distress, known as cardiorenal syndrome, is a common complication of heart failure and causes further medical problems and need for hospitalization. While there are various effective treatments for heart failure, more research is needed to determine the best treatment for targeting both ADHF and cardiorenal syndrome. This study will compare the safety and effectiveness of ultrafiltration versus standard medical drug therapy in improving renal function and relieving fluid buildup in people hospitalized with ADHF and cardiorenal syndrome.

Read the detailed description

Heart failure is a common condition that affects approximately 5 million people in the United States, with 550,000 new cases diagnosed each year. Common symptoms of heart failure include swelling and fluid buildup in the legs, feet, and/or lungs; shortness of breath; coughing; elevated heart rate; change in appetite; and fatigue. If left untreated, the condition of the heart may deteriorate so far that the person undergoes ADHF. The number of hospitalizations attributed to ADHF has risen significantly, with many people readmitted soon after discharge because of recurring symptoms or further medical complications, such as cardiorenal syndrome. Current heart failure treatments focus on removing excess fluid buildup, often by increasing urination with diuretic medications or by draining directly from the veins. Direct drainage from the veins, also known as ultrafiltration, may be the more effective method for treating people with ADHF and cardiorenal syndrome. This study will compare the safety and effectiveness of ultrafiltration versus standard medical drug therapy in improving renal function and relieving fluid buildup in people hospitalized with ADHF and cardiorenal syndrome.

Participation in this study will last 60 days. All potential participants will undergo initial screening, which will include a medical history, physical exam, blood draws, measurements of fluid intake and urine output, and questionnaires. These same evaluations and procedures will be repeated at various points during the hospital stay. Eligible participants will be randomly assigned to receive standard medical drug therapy or fluid removal by ultrafiltration. Standard medical drug therapy will involve the intravenous delivery of diuretics and possibly other doctor-recommended medications. Ultrafiltration will involve intravenously removing blood, passing it through an ultrafiltration device, and then returning the blood to the participant. During ultrafiltration, participants will be treated with a blood thinner through the IV, as well.

Follow-up assessments will occur at Days 30 and 60 after treatment. Follow-up assessments will include measurements of fluid intake, urine output, and vital signs; blood draws; physical exams; and questions about medications and status of recovery.

Conditions
Heart Failure
Being tested
Stepped pharmacologic care, Ultrafiltration
Keywords
Acute Decompensated Heart Failure, Acute Decompensated Heart Failure With Cardiorenal Syndrome, Cardiorenal Syndrome, Persistent Congestion, Ultra Filtration
Medical subject headings
Heart Failure, Cardio-Renal Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stepped pharmacologic careDrug

    Stepped care will provide treating physicians with guidelines for the intensification of diuretic therapy and the possible use of vasodilators and inotropes.

  • UltrafiltrationDevice

    All loop diuretics will be discontinued. Treatment will involve slow continuous ultrafiltration until an optimal volume status has been achieved. Ultrafiltration therapy will be initiated after the placement of appropriate intravenous access and will continue until the participant's signs and symptoms of congestion have been optimized. Fluid status will be managed exclusively by ultrafiltration using the Aquadex system 100 (CHF Solutions, Inc.) according to the manufacturer's specifications. The use of vasodilators or inotropic agents will be prohibited unless deemed necessary for rescue therapy.

Study groups in NCT00608491
Study groupRoleWhat they receive
Stepped pharmacologic careActive comparatorStepped care will provide treating physicians with guidelines for the intensification of diuretic therapy and the possible use of vasodilators and inotropes.
Receives: Drug: Stepped pharmacologic care
UltrafiltrationExperimentalAll loop diuretics will be discontinued. Treatment will involve slow continuous ultrafiltration until an optimal volume status has been achieved. Ultrafiltration therapy will be initiated after the placement of appropriate intravenous access and will continue until the participant's signs and symptoms of congestion have been optimized. Fluid status will be managed exclusively by ultrafiltration using the Aquadex system 100 (CHF Solutions, Inc.) according to the manufacturer's specifications. The use of vasodilators or inotropic agents will be prohibited unless deemed necessary for rescue therapy.
Receives: Device: Ultrafiltration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Serum Creatinine

    Measured: Change from Baseline to Day 4

  2. Change in Weight

    Measured: Change from Baseline to Day 4

Secondary outcomes (68)

  1. Change in Glomerular Filtration Rate

    Measured: Change from Baseline to Day 4

  2. Change in Serum Creatinine

    Measured: Change from Baseline to Day 7

  3. Change in Glomerular Filtration Rate

    Measured: Change from Baseline to Day 7

  4. Changes in Weight

    Measured: Change from Baseline to Day 1

  5. Changes in Weight

    Measured: Change from Baseline to Day 2

  6. Change in Weight

    Measured: Change from Baseline to Day 3

  7. Changes in Weight

    Measured: Change from Baseline to Day 5

  8. Change in Weight

    Measured: Change from Baseline to Day 6

  9. Cumulative Net Fluid Loss

    Measured: Randomization through Day 1

  10. Cumulative Net Fluid Loss

    Measured: Randomization through Day 2

  11. Cumulative Net Fluid Loss

    Measured: Randomization through Day 3

  12. Cumulative Net Fluid Loss

    Measured: Randomization through Day 4

  13. Cumulative Net Fluid Loss

    Measured: Randomization through Day 5

  14. Cumulative Net Fluid Loss

    Measured: Randomization through Day 6

  15. Cumulative Net Fluid Loss

    Measured: Randomization through Day 7

  16. Dyspnea Visual Analog Scale

    Scale range: -100 , +100

    -100=worse, +100=better

    Measured: Change from Baseline to Day 4

  17. Change in Global Visual Analog Scale

    Scale range: -100 , +100

    -100=worse, +100=better Participants asked to mark their global well being on a 10 cm vertical line, with the top labeled "best you have ever felt" and the bottom labeled "worst you have ever felt".

    Measured: Change from Baseline to Day 4

  18. Change in Dyspnea Visual Analog Scale

    Scale range: -100 , +100

    -100=worse, +100=better

    Measured: Baseline to Day 7/Discharge

  19. Change in Global Visual Analog Scale

    Scale range: -100 , +100

    -100=worse, +100=better Participants asked to mark their global well being on a 10 cm vertical line, with the top labeled "best you have ever felt" and the bottom labeled "worst you have ever felt".

    Measured: Baseline to Day 7/Discharge

  20. Change in Furosemide-Equivalent Dose

    Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40)

    Measured: Baseline to Day 7/Discharge

  21. Change in Blood Sodium Level

    Measured: Baseline to Day 4

  22. Change in Blood Potassium Level

    Measured: Baseline to Day 4

  23. Change in Blood Urea Nitrogen/Urea

    Measured: Baseline to Day 4

  24. Change in Blood Bicarbonate Level

    Measured: Baseline to Day 4

  25. Change in Blood Hemoglobin Level

    Measured: Baseline to Day 4

  26. Change in Blood Sodium Level

    Measured: Baseline to Day 7/Discharge

  27. Change in Blood Potassium Level

    Measured: Baseline to Day 7/Discharge

  28. Change in Blood Urea Nitrogen/Urea

    Measured: Baseline to Day 7/Discharge

  29. Change in Blood Bicarbonate Level

    Measured: Baseline to Day 7/Discharge

  30. Change in Blood Hemoglobin Level

    Measured: Baseline to Day 7/Discharge

  31. Change in Blood Cystatin C

    Measured: Baseline to Day 4

  32. Change in Uric Acid

    Measured: Baseline to Day 4

  33. Change in Blood N- Terminal Pro- BNP

    Measured: Baseline to Day 4

  34. Change in Plasma Renin Activity

    Measured: Baseline to Day 4

  35. Change in Blood High Sensitivity Troponin I

    Measured: Baseline to Day 4

  36. Change in Blood Aldosterone

    Measured: Baseline to Day 4

  37. Change in Blood Procollagen III N-terminal Propepide

    Measured: Baseline to Day 4

  38. Change in Blood Endothelin-1

    Measured: Baseline to Day 4

  39. Change in Blood High Sensitivity C-Reactive Protein

    Measured: Baseline to Day 4

  40. Change in Blood Carboxy-terminal Telopeptide of Collagen Type I

    Measured: Baseline to Day 4

  41. Change in Blood Cystatin C

    Measured: Baseline to Day 7/Discharge

  42. Change in Blood Uric Acid

    Measured: Baseline to Day 7/Discharge

  43. Change in Blood N Terminal Pro-Natriuretic Peptide

    Measured: Baseline to Day 7/Discharge

  44. Change in Plasma Renin Activity

    Measured: Baseline to Day 7/Discharge

  45. Change in Blood High Sensitivity Troponin I

    Measured: Baseline to Day 7/Discharge

  46. Change in Blood Aldosterone

    Measured: Baseline to Day 7/Discharge

  47. Change in Blood Procollagen III N-terminal Propepide

    Measured: Baseline to Day 7/Discharge

  48. Change in Blood Endothelin-1

    Measured: Baseline to Day 7/Discharge

  49. Change in Blood Carboxy-terminal Telopeptide of Collagen Type I

    Measured: Baseline to Day 7/Discharge

  50. Change in Blood High Sensitivity C-Reactive Protein

    Measured: Baseline to Day 7/Discharge

  51. Weight Change

    Measured: Baseline to Day 30

  52. Change in Furosemide-Equivalent Dose

    Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40)

    Measured: Baseline to Day 30

  53. Creatinine Change

    Measured: Baseline to Day 30

  54. Glomerular Filtration Rate Change

    Measured: Baseline to Day 30

  55. Weight Change

    Measured: Baseline to Day 60

  56. Change in Furosemide-Equivalent Dose

    Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40)

    Measured: Baseline to Day 60

  57. Best Available Serum Creatinine Change

    Core laboratory when available. If not available, local laboratory results were used.

    Measured: Baseline to Day 60

  58. Best Available Glomerular Filtration Rate Change

    Core laboratory when available. If not available, local laboratory results were used.

    Measured: Baseline to Day 60

  59. Change in Blood Uric Acid

    Measured: Baseline to Day 60

  60. Change in Blood Cystatin C

    Measured: Baseline to Day 60

  61. Change in Blood N Terminal Pro - B Natriuretic Peptides

    Measured: Baseline to Day 60

  62. Change in Plasma Renin Activity

    Measured: Baseline to Day 60

  63. Change in Blood High Sensitivity Troponin I

    Measured: Baseline to Day 60

  64. Change in Blood Aldosterone

    Measured: Baseline to Day 60

  65. Change in Blood Procollagen III N-terminal Propepide

    Measured: Baseline to Day 60

  66. Change in Blood Endothelin-1

    Measured: Baseline to Day 60

  67. Change in Blood High Sensitivity C-Reactive Protein

    Measured: Baseline to Day 60

  68. Change in Blood Carboxy-terminal Telopeptide of Collagen Type I

    Measured: Baseline to Day 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2008 (estimated)
  2. Study startMar 2008
  3. Primary completionMar 2012
  4. Study completionJun 2012

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
188 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00608491
Sponsor's protocol ID
Pro00018064
Other IDs
U01HL084904-04, U01HL084904, 522
Acronym
CARRESS
Status last verified
May 2013
First submitted
25 Jan 2008
Last updated
24 Jun 2013
Data monitoring committee
Yes

Publications

  • Bart BA, Goldsmith SR, Lee KL, Givertz MM, O'Connor CM, Bull DA, Redfield MM, Deswal A, Rouleau JL, LeWinter MM, Ofili EO, Stevenson LW, Semigran MJ, Felker GM, Chen HH, Hernandez AF, Anstrom KJ, McNulty SE, Velazquez EJ, Ibarra JC, Mascette AM, Braunwald E; Heart Failure Clinical Research Network. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012 Dec 13;367(24):2296-304. doi: 10.1056/NEJMoa1210357. Epub 2012 Nov 6.

    PubMed 23131078

  • Rao VS, Ahmad T, Brisco-Bacik MA, Bonventre JV, Wilson FP, Siew ED, Felker GM, Anstrom KK, Mahoney DD, Bart BA, Tang WHW, Velazquez EJ, Testani JM. Renal Effects of Intensive Volume Removal in Heart Failure Patients With Preexisting Worsening Renal Function. Circ Heart Fail. 2019 Jun;12(6):e005552. doi: 10.1161/CIRCHEARTFAILURE.118.005552. Epub 2019 Jun 5.

    PubMed 31163974

  • Kitai T, Grodin JL, Kim YH, Tang WH. Impact of Ultrafiltration on Serum Sodium Homeostasis and its Clinical Implication in Patients With Acute Heart Failure, Congestion, and Worsening Renal Function. Circ Heart Fail. 2017 Feb;10(2):e003603. doi: 10.1161/CIRCHEARTFAILURE.116.003603.

    PubMed 28130379

  • de Denus S, Rouleau JL, Mann DL, Huggins GS, Cappola TP, Shah SH, Keleti J, Zada YF, Provost S, Bardhadi A, Phillips MS, Normand V, Mongrain I, Dube MP. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials. Pharmacogenomics J. 2017 Mar;17(2):192-200. doi: 10.1038/tpj.2016.4. Epub 2016 Mar 1.

    PubMed 26927285

  • Lala A, McNulty SE, Mentz RJ, Dunlay SM, Vader JM, AbouEzzeddine OF, DeVore AD, Khazanie P, Redfield MM, Goldsmith SR, Bart BA, Anstrom KJ, Felker GM, Hernandez AF, Stevenson LW. Relief and Recurrence of Congestion During and After Hospitalization for Acute Heart Failure: Insights From Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS-HF). Circ Heart Fail. 2015 Jul;8(4):741-8. doi: 10.1161/CIRCHEARTFAILURE.114.001957. Epub 2015 Jun 3.

    PubMed 26041600

  • Mentz RJ, Stevens SR, DeVore AD, Lala A, Vader JM, AbouEzzeddine OF, Khazanie P, Redfield MM, Stevenson LW, O'Connor CM, Goldsmith SR, Bart BA, Anstrom KJ, Hernandez AF, Braunwald E, Felker GM. Decongestion strategies and renin-angiotensin-aldosterone system activation in acute heart failure. JACC Heart Fail. 2015 Feb;3(2):97-107. doi: 10.1016/j.jchf.2014.09.003. Epub 2014 Oct 31.

    PubMed 25543972

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Stepped pharmacologic care and Ultrafiltration in people with Heart Failure, run by Duke University at 9 sites in 2 countries.

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 6 inclusion and 18 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: finished, as of the sponsor's last update on 24 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in Serum Creatinine (time frame: Change from Baseline to Day 4). The study lists 2 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 NCT00608491, which also lists 6 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 24 Jun 2013.

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