Protocolized Diuretic Strategy in Cardiorenal Failure

NCT01921829 | Terminated Phase 4 Results DMC

• 1 other identifier: PRO13040071
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is a randomized clinical trial to evaluate if taking diuretics (medications that increase urine production and help with fluid removal from the body) in a standardized fashion (using a guideline for adjusting doses based on measured urine output) could improve health outcomes in patients with cardiorenal failure or cardiorenal syndrome (combined heart and kidney failure) with edema (too much fluid in their arms, legs, and/or lungs). Under usual care, these patients are treated with diuretics and other medications in increasing doses, but not necessarily to maintain a specific amount of urine output per day. Current heart failure (HF) treatment guidelines do not provide any standard protocol, or guideline, for adjusting diuretic doses. At the point when kidney function worsens to the degree that the kidneys are no longer able to respond to the medications used to remove fluid, either ultrafiltration (UF) or dialysis (also called hemodialysis \[HD\]) is typically started in order to remove fluid. In both UF and dialysis, excess fluid is removed from the body by using a machine. In dialysis, both waste products and fluid are removed and electrolyte abnormalities are corrected. In UF, only fluid is removed. Both procedures use the same machine. This study will test whether a Protocolized Diuretic Strategy (ProDiuS), a plan for adjusting diuretic doses based on measured urine output, will improve clinical care for cardiorenal syndrome. Such a plan for adjusting diuretic doses is needed to improve symptoms, decrease the length of hospital stays and rehospitalization rates, and improve health-related quality of life (HRQOL) in cardiorenal syndrome patients.

Conditions

Cardiac Failure; Renal Failure; Kidney Failure

Keywords

Cardiorenal failure; Cardiorenal syndrome; Diuretic resistance; Volume overload; Edema; Health-related quality of life; Outcomes; Treatment protocol

Outcome Measures

Primary Outcomes (1)

• Change in Body Weight (kg) From Randomization to Day 4 or Date of Discharge (Whichever Comes First)

  The change in body weight (kg) from randomization to day 4 or date of discharge will be determined by the difference between body weight at day 4 after randomization or date of discharge (whichever comes first) and body weight taken at baseline measured in the hospital on standard scales without shoes and wearing a hospital gown, measured before breakfast and post-voiding.

  4 days (96 hours)

Secondary Outcomes (19)

• Length of Hospitalization

  1 month

• Number of Rehospitalizations for Heart Failure (HF)

  Up to 3 months (assessed at 1 month and 3 months)

• Number of Total Rehospitalizations

  Up to 3 months (assessed at 1 month and 3 months)

• All-cause Mortality

  Up to 3 months (assessed at 1 month and 3 months)

• Difference From Baseline to 1 Month in Change in Right Internal Jugular Vein (RIJV) Cross-sectional Area (CSA) Pre- and Post-Valsalva

  Up to 1 month (measured at baseline and 1 mo)

Other Outcomes (1)

• Adverse Events

  Daily while in hospital , 1 mo, & 3 mos

Study Arms (2)

Usual Care

NO INTERVENTION

Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.

Protocolized Diuretic Strategy

EXPERIMENTAL

Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is \< 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is \> 5 L/day, diuretic regimen will be reduced.

Drug: Protocolized Diuretic Strategy

Interventions

Protocolized Diuretic Strategy DRUG

The Protocolized Diuretic Strategy will administer diuretics according to an algorithm based on based on the "stepped pharmacologic care arm" used by the CARRESS-HF trial investigators. This algorithm targets a relatively aggressive goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide).

Also known as: Diuretic Treatment Protocol, Stepped Pharmacologic Care

Protocolized Diuretic Strategy

Eligibility Criteria

• Age: 21 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥21 years
• History of heart failure (HF), with either left ventricular (LV) dysfunction (EF\<40%) or at least stage I diastolic or right ventricular (RV) dysfunction based on echocardiogram (ECHO) within the last year or diagnosis of HF by International Classification of Diseases (ICD-9)
• Evidence of renal dysfunction based on one of the following:
• Estimated glomerular filtration rate (GFR) 15-59 mL/min/1.73 m2 based on the Modification of Diet in Renal Disease (MDRD) equation using serum creatinine (Cr) obtained within 6 months of admission
• Elevated Cr above upper limits of normal
• An increase in serum Cr of ≥0.3 mg/dL or ≥50% from baseline on admission or during diuretic therapy, with no alternative cause for worsening renal function, while demonstrating signs and symptoms of persistent volume overload occurring within 7 days before admission or during hospitalization
• Evidence of volume overload by clinical and/or radiographic features, with at least 2 of the following: 1) peripheral edema ≥2+; 2) jugular venous distension ≥7 cm; 3) radiographic pulmonary edema or pleural effusion; 4) enlarged liver or ascites; 5) pulmonary rales, paroxysmal nocturnal dyspnea, or orthopnea; 6) elevated brain natriuretic peptide (BNP) level; 7) documentation of elevated right heart filling pressures by pulmonary artery catheter or right heart catheterization

You may not qualify if:

• Use of inotropes (at time of screening)
• Acute indications for hemodialysis (HD) (e.g., severe hyperkalemia, metabolic acidosis, uremic signs or symptoms, pericardial friction rub)
• Specific forms of HF by chart diagnoses:
• Congenital heart disease
• Primary valvular heart disease due to severe valvular stenosis or acute severe valvular regurgitation or valvular disease requiring immediate surgical repair
• Infiltrative cardiomyopathies
• Pulmonary hypertension (PH) as defined by World Health Organization (WHO) group I and WHO group IV - Prior use of ultrafiltration (UF) or HD in the 3 months preceding hospitalization
• End-stage renal disease (ESRD) requiring chronic dialysis or estimated GFR \<15 mL/min/1.73 m2 by MDRD equation (i.e., pre-existing ESRD)
• Prior cardiac or kidney transplantation
• Intravascular volume depletion based on clinical assessment
• Cardiogenic shock and/or systolic blood pressure (SBP) \<90 mmHg
• Unstable coronary disease or acute coronary syndrome within 1 month of admission
• Alternative explanation for worsening renal function (e.g., obstructive nephropathy, contrast-induced nephropathy, acute tubular necrosis, intrinsic renal diseases)
• Life expectancy \< 3 months due to other chronic health conditions (e.g., end-stage liver disease, pulmonary disease, malignancy, etc.)
• Psychiatric disorder requiring admission to a psychiatric hospital during HF admission

Sponsors & Collaborators

• Kelly V. Liang, MD: lead

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• 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.

  PMID: 23131078 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Renal Insufficiency; Cardio-Renal Syndrome; Edema

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Dr. Kelly Liang
• Organization: University of Pittsburgh

liangk@upmc.edu

507-269-7812

Study Officials

• Kelly V Liang, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 23, 2013
• First Posted: August 13, 2013
• Study Start: November 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: August 21, 2017
• Results First Posted: July 17, 2017

Record last verified: 2017-07

Locations

US (1)