Cardiac FailurePhase 4ProDiuSNCT01921829
Protocolized Diuretic Strategy in Cardiorenal Failure
A Phase 4 study testing Protocolized Diuretic Strategy in people with Cardiac Failure and Renal Failure, run by Kelly V. Liang, MD at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 years and older, men only
- Conditions the study is for
- Cardiac Failure, Renal Failure, Kidney Failure
- What is being tested?
- Protocolized Diuretic Strategy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2013to Nov 2015
- Phase
- Phase 4
- 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 21 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
- Previous enrollment in this trial or other diuretic or UF trial in the prior 3 months
- Expected geographic unavailability for 3 months following hospital admission
- Pregnancy
- Inability to provide informed consent
- Physician's assessment that use of the protocol could be unsafe or lead to adverse consequences for the patient
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Effect of Protocolized Diuretic Strategy on Clinical Outcomes and Health-related Quality of Life in Cardiorenal Failure: A Randomized Trial
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.
Read the detailed description
Heart failure (HF) accounts for over 1 million hospital admissions annually in the United States and is a leading cause of disability and healthcare costs. Cardiorenal syndrome and worsening renal function are independent risk factors for morbidity and mortality in HF. Effective fluid removal, manifested by a decrease in body weight, is one of the most important goals of treatment in cardiorenal syndrome. Current medical therapeutic options, including sodium and fluid restriction, diuretics, blockade of the renin-angiotensin-aldosterone system, inotropes, and nesiritide, are suboptimal in patients with advanced cardiorenal syndrome. When medical therapies fail, ultrafiltration (UF) may be used for mechanical fluid removal using dialysis or UF machines. UF can effectively remove fluid in HF patients, but its precise role in the therapy of cardiorenal syndrome is still unclear. A multicenter randomized controlled trial (CARRESS-HF) suggested that UF was not superior to a stepped pharmacologic diuretic regimen, with a similar amount of weight loss with the two approaches and a higher rate of adverse events in the UF group. Therefore, a protocolized diuretic strategy is needed that is superior to current clinical care in the management of cardiorenal syndrome.
Current HF guidelines do not provide any standard protocol for diuretic dosing. The variation in usual clinical care may explain the long hospital stays and worsening renal function common in these patients. One retrospective observational study compared a diuretic dosing protocol to usual diuretic therapy for patients admitted with acute decompensated HF. Protocol diuretic use was associated with greater weight loss and significantly lower risk of 30-day readmission. However, due to its retrospective design, the baseline characteristics of the two groups differed in many pertinent covariates, and its generalizability is limited.
The proposed study aims to determine if a protocolized diuretic treatment strategy, as opposed to usual clinical care, results in improved clinical decongestion, clinical outcomes, and health-related quality of life (HRQOL), while preserving renal function in hospitalized patients with cardiorenal syndrome. It is a prospective randomized single-blind trial with equal allocation (1:1) and random block randomization of 150 participants hospitalized at University of Pittsburgh Medical Center (UPMC) for cardiorenal syndrome recruited over 3 years (approximately 50 participants/year). Participants with cardiorenal syndrome will be randomized to a Protocolized Diuretic Strategy (based on the stepped pharmacologic algorithm used in the CARRESS-HF trial) vs. Usual Care. Participants will be followed daily in the hospital during the treatment period, as well as at 1-month and 3-month follow-up visits in the outpatient HF clinic.
Primary Research Question:
- In hospitalized patients with cardiorenal syndrome, does a protocolized diuretic treatment strategy, as opposed to usual clinical care, result in improved clinical decongestion based on change in body weight at day 4 or hospital discharge (whichever comes first)? Primary Hypothesis. In hospitalized patients with cardiorenal syndrome, protocolized diuretic therapy will result in greater reduction in body weight and improved clinical decongestion compared to usual care.
Secondary Research Questions:
- Do clinical outcomes, including length of hospitalization, number of rehospitalizations for HF, and mortality, improve after protocolized diuretic therapy compared to usual care over 3 months? Hypothesis 1. Protocolized diuretic therapy will be associated with reduced length of hospital stay, decreased rehospitalization rates, and decreased mortality, compared to usual care.
- Do other measures of volume status improve after protocolized diuretic therapy compared to usual care during hospitalization and over 3 months? Hypothesis 2. Protocolized diuretic therapy will be associated with greater decongestion based on increased venous compliance of the internal jugular vein (via Doppler ultrasound), negative fluid balance, and clinical decongestion, compared to usual care.
- Do HRQOL outcomes improve after protocolized diuretic therapy compared to usual care over 3 months? Hypothesis 3. HRQOL indices in physical well-being, mental well-being, and sleep quality domains will improve after protocolized diuretic therapy compared to usual care.
- Do renal outcomes (safety endpoints), including renal function changes and need for UF or renal replacement therapy, differ between protocolized diuretic therapy and usual care during hospitalization and over 3 months? Hypothesis 4. Protocolized diuretic therapy will be superior to usual care in terms of worsening renal function and need for UF or renal replacement therapy.
Subgroup Research Questions:
- Do outcomes differ between the Protocolized Diuretic Strategy vs. Usual care stratified by type of heart failure (e.g., systolic dysfunction (EF <40%) vs. diastolic dysfunction (EF ≥40%); ischemic vs. other; none-mild vs. moderate-severe mitral regurgitation (MR) or tricuspid regurgitation (TR))? Hypothesis 1. No difference will be seen between treatment and control groups based on type of heart failure.
This trial is of utmost interest to cardiologists and nephrologists, who struggle to find the optimal diuretic and medical management strategy to effectively remove excess fluid yet preserve renal function. It is highly relevant to many clinicians and the community at large, as HF and cardiorenal syndrome are a leading cause of hospitalizations and healthcare costs. If a protocolized diuretic strategy can be found that optimally removes fluid in an efficient and safe manner, it could potentially be disseminated to community physicians and/or incorporated into public policy or HF treatment guidelines in order to improve quality of care and reduce healthcare costs in this population with high morbidity and mortality.
- Conditions
- Cardiac Failure, Renal Failure, Kidney Failure
- Being tested
- Protocolized Diuretic Strategy
- Keywords
- Cardiorenal failure, Cardiorenal syndrome, Diuretic resistance, Volume overload, Edema, Health-related quality of life, Outcomes, Treatment protocol
- Medical subject headings
- Heart Failure, Renal Insufficiency, Cardio-Renal Syndrome, Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protocolized Diuretic StrategyDrug
Also called Diuretic Treatment Protocol, Stepped Pharmacologic Care
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Protocolized Diuretic Strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 days (96 hours)
Secondary outcomes (19)
Length of Hospitalization
Length of hospitalization will be ascertained from admission date to date of discharge.
Measured: 1 month
Number of Rehospitalizations for Heart Failure (HF)
Number of rehospitalizations for HF will be ascertained based on chart review of admissions with HF as a coded diagnosis, evidence of clinical volume overload, and treatment with intravenous diuretics.
Measured: Up to 3 months (assessed at 1 month and 3 months)
Number of Total Rehospitalizations
Number of rehospitalizations will be ascertained based on chart review of admissions to any hospital after the index hospitalization
Measured: Up to 3 months (assessed at 1 month and 3 months)
All-cause Mortality
All-cause mortality will be ascertained based on chart review of vital status (alive/dead) and cause of death.
Measured: 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
The change in cross-sectional area (CSA) of the right internal jugular vein (RIJV) pre- and post-Valsalva is a measurement of venous compliance and was determined noninvasively with Doppler ultrasound. An increase in RIJV CSA >17% during Valsalva effectively rules out elevated right atrial pressure (RAP) and suggests effective volume removal or decongestion. The difference between baseline and 1 month values of change in RIJV CSA are reported.
Measured: Up to 1 month (measured at baseline and 1 mo)
Fluid Balance
Strict intake (oral intake, intravenous medications, fluids, etc.) and output (urine, emesis, stools, drains, etc.) will be documented by the nurses on the HF floors per routine clinical protocol for all patients. Fluid balance will be determined by subtracting the volume of total intake from the volume of total output (in mL) over 24 hours (7 am to 7 am or the preceding 24-h period if no 7 am to 7 am period is available). Fluid balance and urine output will be ascertained by chart review daily during the intervention while the participants are hospitalized.
Measured: Daily while in hospital
Acute Kidney Injury
Acute kidney injury will be defined based a rise in Cr ≥0.3 mg/dL.
Measured: Daily while in hospital, 1 mo & 3 mos
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score Change at 1 Month
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a well-validated 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A mean difference over time of 5 points on the KCCQ Overall Summary Scale reflects a clinically significant change in heart failure status. A 10 point decline in KCCQ scores has important prognostic significance in terms of survival.
Measured: Baseline to 1 month
Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score Change at 1 Month
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a well-validated 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A mean difference over time of 5 points on the KCCQ Overall Summary Scale reflects a clinically significant change in heart failure status. A 10 point decline in KCCQ scores has important prognostic significance in terms of survival.
Measured: Baseline to 1 month
SF-36 Mental Component Score (MCS) Change at 1 Month
The Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) is a well-validated generic HRQOL questionnaire that generates two composite scores: the Physical Component Score (PCS) and Mental Component Score (MCS). The PCS aggregates items from Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, and Social Functioning. The MCS aggregates items from Role-Emotional, Mental Health, General Health, Vitality, and Social Functioning. The mean for each summary scale is 50 points with standard deviation of 10 points. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: Baseline to 1 month
SF-36 Physical Component Score (PCS) Change at 1 Month
The Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) is a well-validated generic HRQOL questionnaire that generates two composite scores: the Physical Component Score (PCS) and Mental Component Score (MCS). The PCS aggregates items from Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, and Social Functioning. The MCS aggregates items from Role-Emotional, Mental Health, General Health, Vitality, and Social Functioning. The mean for each summary scale is 50 points with standard deviation of 10 points. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: Baseline to 1 month
PHQ-9 Depression Index Change at 1 Month
The Patient Health Questionnaire (PHQ-9) Depression Index is a well-established index of depression and has been validated in many patient populations. Its scores range from 0-27 with increasing scores representing increasing depression severity. Score categories represent depression severity and management recommendations:
0-4 - Minimal or no depression. Monitor; may not require treatment. 5-9 - Mild. Use clinical judgment (symptom duration, functional impairment) to determine necessity of treatment.
10-14 - Moderate. Use clinical judgment (symptom duration, functional impairment) to determine necessity of treatment.
15-19 - Moderately severe. Warrants active treatment with psychotherapy, medications, or combination.
20-27 - Severe. Warrants active treatment with psychotherapy, medications, or combination.
Measured: Baseline to 1 month
PSQI Total Score Change at 1 Month
The Pittsburgh Sleep Quality Index (PSQI) is the most widely used global sleep assessment and has been studied in the renal transplant population. Consisting of 19 items, the PSQI measures several different aspects of sleep, offering seven component scores and one composite score. The component scores consist of subjective sleep quality, sleep latency (i.e., how long it takes to fall asleep), sleep duration, habitual sleep efficiency (i.e., the percentage of time in bed that one is asleep), sleep disturbances, use of sleeping medication, and daytime dysfunction. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. Traditionally, the items from the PSQI have been summed to create a total score to measure overall sleep quality.
Measured: Baseline to 1 month
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score Change at 3 Months
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a well-validated 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A mean difference over time of 5 points on the KCCQ Overall Summary Scale reflects a clinically significant change in heart failure status. A 10 point decline in KCCQ scores has important prognostic significance in terms of survival.
Measured: Baseline to 3 months
Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score Change at 3 Months
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a well-validated 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A mean difference over time of 5 points on the KCCQ Overall Summary Scale reflects a clinically significant change in heart failure status. A 10 point decline in KCCQ scores has important prognostic significance in terms of survival.
Measured: Baseline to 3 months
SF-36 Mental Component Score (MCS) Change at 3 Months
The Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) is a well-validated generic HRQOL questionnaire that generates two composite scores: the Physical Component Score (PCS) and Mental Component Score (MCS). The PCS aggregates items from Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, and Social Functioning. The MCS aggregates items from Role-Emotional, Mental Health, General Health, Vitality, and Social Functioning. The mean for each summary scale is 50 points with standard deviation of 10 points. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: Baseline to 3 months
SF-36 Physical Component Score (PCS) Change at 3 Months
The Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) is a well-validated generic HRQOL questionnaire that generates two composite scores: the Physical Component Score (PCS) and Mental Component Score (MCS). The PCS aggregates items from Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, and Social Functioning. The MCS aggregates items from Role-Emotional, Mental Health, General Health, Vitality, and Social Functioning. The mean for each summary scale is 50 points with standard deviation of 10 points. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: Baseline to 3 months
PHQ-9 Depression Index Change at 3 Months
The Patient Health Questionnaire (PHQ-9) Depression Index is a well-established index of depression and has been validated in many patient populations. Its scoring ranges from 0-27 with increasing scores representing increasing depression severity. Score categories determine depression severity and recommended management:
0-4 - Minimal or none. Monitor; may not require treatment. 5-9 - Mild. Use clinical judgment (symptom duration, functional impairment) to determine necessity of treatment.
10-14 - Moderate. Use clinical judgment (symptom duration, functional impairment) to determine necessity of treatment.
15-19 - Moderately severe. Warrants active treatment with psychotherapy, medications, or combination.
20-27 - Severe. Warrants active treatment with psychotherapy, medications, or combination.
Measured: Baseline to 3 months
PSQI Total Score Change at 3 Months
The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over a 1-month time interval. The measure consists of 19 individual items, creating 7 components that produce one global score, and takes 5-10 minutes to complete. Consisting of 19 items, the PSQI measures several different aspects of sleep, offering seven component scores and one composite score. The component scores consist of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. Traditionally, the items from the PSQI have been summed to create a total score to measure overall sleep quality.
Measured: Baseline to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2013 (estimated)
- Study startNov 2013
- Primary completionNov 2015
- Study completionNov 2015
Why it stopped: Due to futility due to lower than expected recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiac 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kelly V. Liang, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kelly V. Liang, MD, University of Pittsburgh
- Investigators
- Kelly V Liang, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01921829
- Sponsor's protocol ID
- PRO13040071
- Acronym
- ProDiuS
- Status last verified
- Jul 2017
- First submitted
- 23 Jul 2013
- Last updated
- 21 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- 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
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Protocolized Diuretic Strategy on Clinical Outcomes and Health-related Quality of Life in Cardiorenal Failure: A Randomized Trial
- ClinicalTrials.gov ID
- NCT01921829
- Acronym / sponsor ID
- ProDiuS / PRO13040071
- 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
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to futility due to lower than expected recruitment
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Kelly V. Liang, MDUniversity, hospital or other
- Study start
- Nov 2013
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 13 Aug 2013 (estimated)
- Results
- Posted 17 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Heart failure (HF) accounts for over 1 million hospital admissions annually in the United States and is a leading cause of disability and healthcare costs. Cardiorenal syndrome and worsening renal function are independent risk factors for morbidity and mortality in HF. Effective fluid removal, manifested by a decrease in body weight, is one of the most important goals of treatment in cardiorenal syndrome. Current medical therapeutic options, including sodium and fluid restriction, diuretics, blockade of the renin-angiotensin-aldosterone system, inotropes, and nesiritide, are suboptimal in patients with advanced cardiorenal syndrome. When medical therapies fail, ultrafiltration (UF) may be used for mechanical fluid removal using dialysis or UF machines. UF can effectively remove fluid in HF patients, but its precise role in the therapy of cardiorenal syndrome is still unclear. A multicenter randomized controlled trial (CARRESS-HF) suggested that UF was not superior to a stepped pharmacologic diuretic regimen, with a similar amount of weight loss with the two approaches and a higher rate of adverse events in the UF group. Therefore, a protocolized diuretic strategy is needed that is superior to current clinical care in the management of cardiorenal syndrome.
Current HF guidelines do not provide any standard protocol for diuretic dosing. The variation in usual clinical care may explain the long hospital stays and worsening renal function common in these patients. One retrospective observational study compared a diuretic dosing protocol to usual diuretic therapy for patients admitted with acute decompensated HF. Protocol diuretic use was associated with greater weight loss and significantly lower risk of 30-day readmission. However, due to its retrospective design, the baseline characteristics of the two groups differed in many pertinent covariates, and its generalizability is limited.
The proposed study aims to determine if a protocolized diuretic treatment strategy, as opposed to usual clinical care, results in improved clinical decongestion, clinical outcomes, and health-related quality of life (HRQOL), while preserving renal function in hospitalized patients with cardiorenal syndrome. It is a prospective randomized single-blind trial with equal allocation (1:1) and random block randomization of 150 participants hospitalized at University of Pittsburgh Medical Center (UPMC) for cardiorenal syndrome recruited over 3 years (approximately 50 participants/year). Participants with cardiorenal syndrome will be randomized to a Protocolized Diuretic Strategy (based on the stepped pharmacologic algorithm used in the CARRESS-HF trial) vs. Usual Care. Participants will be followed daily in the hospital during the treatment period, as well as at 1-month and 3-month follow-up visits in the outpatient HF clinic.
Primary Research Question:
- In hospitalized patients with cardiorenal syndrome, does a protocolized diuretic treatment strategy, as opposed to usual clinical care, result in improved clinical decongestion based on change in body weight at day 4 or hospital discharge (whichever comes first)? Primary Hypothesis. In hospitalized patients with cardiorenal syndrome, protocolized diuretic therapy will result in greater reduction in body weight and improved clinical decongestion compared to usual care.
Secondary Research Questions:
- Do clinical outcomes, including length of hospitalization, number of rehospitalizations for HF, and mortality, improve after protocolized diuretic therapy compared to usual care over 3 months? Hypothesis 1. Protocolized diuretic therapy will be associated with reduced length of hospital stay, decreased rehospitalization rates, and decreased mortality, compared to usual care.
- Do other measures of volume status improve after protocolized diuretic therapy compared to usual care during hospitalization and over 3 months? Hypothesis 2. Protocolized diuretic therapy will be associated with greater decongestion based on increased venous compliance of the internal jugular vein (via Doppler ultrasound), negative fluid balance, and clinical decongestion, compared to usual care.
- Do HRQOL outcomes improve after protocolized diuretic therapy compared to usual care over 3 months? Hypothesis 3. HRQOL indices in physical well-being, mental well-being, and sleep quality domains will improve after protocolized diuretic therapy compared to usual care.
- Do renal outcomes (safety endpoints), including renal function changes and need for UF or renal replacement therapy, differ between protocolized diuretic therapy and usual care during hospitalization and over 3 months? Hypothesis 4. Protocolized diuretic therapy will be superior to usual care in terms of worsening renal function and need for UF or renal replacement therapy.
Subgroup Research Questions:
- Do outcomes differ between the Protocolized Diuretic Strategy vs. Usual care stratified by type of heart failure (e.g., systolic dysfunction (EF <40%) vs. diastolic dysfunction (EF ≥40%); ischemic vs. other; none-mild vs. moderate-severe mitral regurgitation (MR) or tricuspid regurgitation (TR))? Hypothesis 1. No difference will be seen between treatment and control groups based on type of heart failure.
This trial is of utmost interest to cardiologists and nephrologists, who struggle to find the optimal diuretic and medical management strategy to effectively remove excess fluid yet preserve renal function. It is highly relevant to many clinicians and the community at large, as HF and cardiorenal syndrome are a leading cause of hospitalizations and healthcare costs. If a protocolized diuretic strategy can be found that optimally removes fluid in an efficient and safe manner, it could potentially be disseminated to community physicians and/or incorporated into public policy or HF treatment guidelines in order to improve quality of care and reduce healthcare costs in this population with high morbidity and mortality.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: Protocolized Diuretic StrategyParticipants 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- 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
Key exclusion criteria (20 listed)
- 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:
- 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
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 |
|---|---|---|
| Protocolized Diuretic StrategyAlso: Diuretic Treatment Protocol, Stepped Pharmacologic CareThe 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). | Drug | Protocolized Diuretic Strategy |
Primary outcome
Change in Body Weight (kg) From Randomization to Day 4 or Date of Discharge (Whichever Comes First)
Time frame: 4 days (96 hours)
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.
19 secondary outcomes
Length of Hospitalization
Time frame: 1 month
Number of Rehospitalizations for Heart Failure (HF)
Time frame: Up to 3 months (assessed at 1 month and 3 months)
Number of Total Rehospitalizations
Time frame: Up to 3 months (assessed at 1 month and 3 months)
All-cause Mortality
Time frame: 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
Time frame: Up to 1 month (measured at baseline and 1 mo)
Fluid Balance
Time frame: Daily while in hospital
Acute Kidney Injury
Time frame: Daily while in hospital, 1 mo & 3 mos
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score Change at 1 Month
Time frame: Baseline to 1 month
Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score Change at 1 Month
Time frame: Baseline to 1 month
SF-36 Mental Component Score (MCS) Change at 1 Month
Time frame: Baseline to 1 month
SF-36 Physical Component Score (PCS) Change at 1 Month
Time frame: Baseline to 1 month
PHQ-9 Depression Index Change at 1 Month
Time frame: Baseline to 1 month
PSQI Total Score Change at 1 Month
Time frame: Baseline to 1 month
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score Change at 3 Months
Time frame: Baseline to 3 months
Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score Change at 3 Months
Time frame: Baseline to 3 months
SF-36 Mental Component Score (MCS) Change at 3 Months
Time frame: Baseline to 3 months
SF-36 Physical Component Score (PCS) Change at 3 Months
Time frame: Baseline to 3 months
PHQ-9 Depression Index Change at 3 Months
Time frame: Baseline to 3 months
PSQI Total Score Change at 3 Months
Time frame: Baseline to 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23131078Bart 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.
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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.
Kelly V Liang, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Protocolized Diuretic Strategy in people with Cardiac Failure and Renal Failure, run by Kelly V. Liang, MD at 1 site in United States.
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 7 inclusion and 20 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: stopped early, as of the sponsor's last update on 21 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 17 Jul 2017). 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 Body Weight (kg) From Randomization to Day 4 or Date of Discharge (Whichever Comes First) (time frame: 4 days (96 hours)). 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 NCT01921829, which also lists 1 linked publication.
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 21 Aug 2017.