- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02644057
Dobutamaine Versus Milrinone in Cardiorenal Syndrome (DOMICAS)
Comparison of Dobutamine Versus Milrinone for Renal Recovery in Patients With Cardiorenal Syndrome-A Prospective Cohort Study in Patients With Acute Decompensated Heart Failure
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Heart failure is recognized as one of the most common indications for hospitalization amongst adults aged >65 years in United States with estimated Medicare cost to be 17billion or more. Chronic heart failure is one of the most life threatening cardiovascular disorder thought to affect nearly six million US population with annual death rate being 600,000. Cardiorenal syndrome although not completely understood in its full context - is a term coined for disorder of the heart and kidneys whereby acute or chronic dysfunction of one precipitates acute or chronic dysfunction of the other. Concomitant kidney failure amongst patients with acute decompensated heart failure is commonly observed . Direct and indirect effects of heart failure other than hemodynamic insult have been identified as primers for acute kidney injury and dysfunction. Patients with preexisting underlying renal disease are more likely to develop worsening renal failure in the setting of ADHF with venous congestion being the most important hemodynamic factor driving it. Worsening renal function defined as increase in serum creatinine of >0.3mg/dl from baseline occurs in 20-30% of patients with ADHF and is associated with greater length of hospital stay, hospital readmission and death. The treatment of ADHF which includes the step up intravenous diuretic therapy in addition to optimizing baseline medicines is limited frequently by diuretic resistance and worsening creatinine level precluding use of Angiotensin converting enzyme inhibitors (ACEi), Angiotensin Receptor Blocking Agents (ARBs), and Spironolactone. Ultrafiltration/Aquapheresis still remains an option for treating non-responders to medical therapy. Inotropes have been known to produce a beneficial hemodynamic effect on heart and lead to better titration to oral regimen. Short term continous intravenous infusion of inotropic agents in patients with documented severe systolic dysfunction who present with significantly depressed cardiac output to maintain end organ perfusion has been shown to be beneficial as per the ACC/AHA guidelines 2013 for management of heart failure. The use of intravenous inotropes remains still a controversial topic in terms of its short lived and long term efficacy on renal recovery in acute decompensated heart failure. In view of the large proportion of patients admitted with acute decompensated heart failure and no real world studies comparing different inotropes to improve kidney function, the investigators aim to compare the efficacy of dobutamine and milrinone in improving kidney function and also their effect on length of stay, symptomatic improvement and medication optimisation
- The primary objective of the study is to objectively measure the response of dobutamine vs milrinone for renal recovery in patients with cardiorenal syndrome (>0.3mg/dl increase in creatinine from baseline) admitted for acute decompensated heart failure. These objective measures include change in serum creatinine, change in weight.
- The secondary objectives are to measure the length of hospitalization, readmission rates and unscheduled visits to the clinic or ER during 60 day follow up period. The investigators will also measure changes in symptoms which will be assessed using global and dyspnea visual analog scale every 24 hours until the patient is discharged .
- The secondary objectives also include to measure diuretic dose, medicine optimization including initiation of beta blocker / ace inhibitors before discharge, at 30 days and 60 days interval
- The investigators will subdivide the patients into ischemic versus non ischemic at the end of trial to see the response in both these categories of patients
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
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New York
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Brooklyn, New York, United States, 11219
- Maimonides Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age >18 years
- Admitted to the hospital with a primary diagnosis of Decompensated Heart Failure
- Onset of cardio-renal syndrome (increasing creatinine>0.3mg/dl) after or before hospitalization. After hospitalization within 7 days of from the time of admission after receiving intravenous diuretics and heart failure medication optimization. Before hospitalization in the setting of escalating doses of outpatient loop diuretics and heart failure medication optimization
Persistent volume overload- For patients with a pulmonary artery catheter, peristent volume overload will include :
Pulmonary capillary wedge pressure >22mm Hg and one of the following clinical signs :2+ peripheral edema and/or pulmonary edema or pleural effusion on chest Xray. For patients without a pulmonary artery catheter- persistent volume overload will include atleast 2 of the following: 2+ peripheral edema , jugular venous pressure >10 mm Hg and pulmonary edema or pleural effusion on chest Xray
- BNP>400
- Cr-1.2-3.0
Exclusion Criteria:
- Intravascular volume depletion
- Acute coronary syndrome within 4 weeks
- Indication for hemodialysis
- Systolic Blood pressure <90mm Hg or MAP<60mm Hg at the time of enrollment
- Alternate explanation for worsening renal function , such as obstructive nephropathy , contrast induced nephropathy , ATN
- Clinical instability likely to require the addition of intravenous vasoactive drugs including vasodilators and/or inotropic drugs
- The use of iodinated radio-contrast material in the past 72 hours or anticipated use of intravenous contrast during the current hospitalization
- Underlying rhythm disorder
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: M-group
Will be given milrinone as an intravenous infusion at 0.2-0.6 mcg/kg/min for a maximum period of 72 hours and adjusted based on creatinine clearance measured by cockcroft-gault equation.
It would be titrated based on hemodynamic response , urine output and at the discretion of the treating physician
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Patients who meet the inclusion criteria for the study will receive milrinone and patients will be monitored for improvement of the renal function objectively with measures such as Blood urea nitrogen, creatinine , daily urine output and changes in weight
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Active Comparator: D-group
Will be given dobutamine as an intravenous infusion at a maximum rate of 20 mcg/kg/min depending on patient tolerance and would adjusted based on hemodynamic response, urine output and at the discretion of treating physician
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Patients who meet the inclusion criteria for the study will receive dobutamine and patients will be monitored for improvement of the renal function objectively with measures such as Blood urea nitrogen, creatinine , daily urine output and changes in weight
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Serum creatinine measured in mg/dl(milligram/decilitre)
Time Frame: Serum Creatinine would be measured every 24 hours in mg/dl from the time of enrollment in the study and will be measured every 24 hours up to a maximum period of 14 days
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Serum Creatinine would be measured every 24 hours in mg/dl from the time of enrollment in the study and will be measured every 24 hours up to a maximum period of 14 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Length of hospitalisation
Time Frame: Length of stay measured in days up to a maximum of 30 days
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Length of stay will start from the day patient is admitted up to a maximum of 30 days
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Length of stay measured in days up to a maximum of 30 days
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Readmission rate
Time Frame: Readmissions would be assessed for a period of 90 days
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Readmissions would be assessed for a period of 90 days
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Global visual analog score
Time Frame: Every 24 hours from the day of enrollment in the study up to a maximum period of 14 days
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Every 24 hours from the day of enrollment in the study up to a maximum period of 14 days
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Dyspnea visual analog score
Time Frame: Every 24 hours starting from the day of enrollment in the study up to a maximum period of 14 days
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Every 24 hours starting from the day of enrollment in the study up to a maximum period of 14 days
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Urine output measured in milliliters in a 24 hour period
Time Frame: Every 24 hours from the day of enrollment in the study up to a maximum period of 14 days
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Urine output would be strictly monitored in millilitres /24 hours starting from the day of enrollment in the study till the patient is discharged from the hospital
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Every 24 hours from the day of enrollment in the study up to a maximum period of 14 days
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Norbert Moskovits, MD, Maimonides Medical Center
- Principal Investigator: Karan Wats, MBBS, Maimonides Medical Center
- Principal Investigator: Syeda A Batul, MBBS, Maimonides Medical Center
Publications and helpful links
General Publications
- Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008 Nov 4;52(19):1527-39. doi: 10.1016/j.jacc.2008.07.051.
- Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, LeJemtel TH, Cheng ML, Wynne J; ADHERE Scientific Advisory Committee and Investigators; ADHERE Study Group. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol. 2005 Jul 5;46(1):57-64. doi: 10.1016/j.jacc.2005.03.051.
- Cuffe MS, Califf RM, Adams KF Jr, Benza R, Bourge R, Colucci WS, Massie BM, O'Connor CM, Pina I, Quigg R, Silver MA, Gheorghiade M; Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) Investigators. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA. 2002 Mar 27;287(12):1541-7. doi: 10.1001/jama.287.12.1541.
- Elkayam U, Tasissa G, Binanay C, Stevenson LW, Gheorghiade M, Warnica JW, Young JB, Rayburn BK, Rogers JG, DeMarco T, Leier CV. Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure. Am Heart J. 2007 Jan;153(1):98-104. doi: 10.1016/j.ahj.2006.09.005.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Kidney Diseases
- Urologic Diseases
- Disease
- Renal Insufficiency
- Heart Failure
- Syndrome
- Cardio-Renal Syndrome
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Platelet Aggregation Inhibitors
- Protective Agents
- Adrenergic Agonists
- Cardiotonic Agents
- Phosphodiesterase Inhibitors
- Adrenergic beta-Agonists
- Sympathomimetics
- Adrenergic beta-1 Receptor Agonists
- Phosphodiesterase 3 Inhibitors
- Milrinone
- Dobutamine
Other Study ID Numbers
- 2015-05-11-MMC
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