Dobutamaine Versus Milrinone in Cardiorenal Syndrome

NCT02644057 | Withdrawn Phase 2

• 1 other identifier: 2015-05-11-MMC
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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 17 billion or more. Chronic heart failure is one of the most life threatening cardiovascular disorder thought to affect nearly six million US population with 600,000 new cases every year. The heart is responsible for perfusion to all vital organs including kidneys and dysfunction in either affects both the vital organs. When dysfunction of heart leads to dysfunction of kidneys or vice versa it is referred to as cardio renal syndrome (CRS). The underlying pathophysiology for CRS has been poorly understood and considered multifactorial. 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. A number of interventions have been used including giving diuretics which helps in decongestion and helps the heart pump blood more effectively. Sometimes these therapies are not effective and may even lead to worsening of renal function. In such cases , inotrope agents which increase the contractility of the heart have been used to help pump more blood to vital organs. There have been very few trials assessing the efficacy of these agents for improving kidney function .The investigators aim to assess the renal recovery with two such agents - dobutamine and milrinone in patients with cardiorenal syndrome who are coming with acute decompensated heart failure

Conditions

Cardiorenal Syndrome

Outcome Measures

Primary Outcomes (1)

• Serum creatinine measured in mg/dl(milligram/decilitre)

  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

Secondary Outcomes (5)

• Length of hospitalisation

  Length of stay measured in days up to a maximum of 30 days

• Readmission rate

  Readmissions would be assessed for a period of 90 days

• Global visual analog score

  Every 24 hours from the day of enrollment in the study up to a maximum period of 14 days

• Dyspnea visual analog score

  Every 24 hours starting from the day of enrollment in the study up to a maximum period of 14 days

• Urine output measured in milliliters in a 24 hour period

  Every 24 hours from the day of enrollment in the study up to a maximum period of 14 days

Study Arms (2)

M-group

ACTIVE COMPARATOR

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

Drug: Milrinone

D-group

ACTIVE COMPARATOR

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

Drug: Dobutamine

Interventions

Milrinone DRUG

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

M-group

Dobutamine DRUG

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

D-group

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maimonides Medical Center: lead

Study Sites (1)

Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

Related Publications (4)

• 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.

  PMID: 19007588 BACKGROUND

• 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.

  PMID: 15992636 BACKGROUND

• 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.

  PMID: 11911756 BACKGROUND

• 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.

  PMID: 17174645 BACKGROUND

MeSH Terms

Conditions

Cardio-Renal Syndrome

Interventions

Milrinone; Dobutamine

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Failure; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Amrinone; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Catecholamines; Phenethylamines; Ethylamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Norbert Moskovits, MD

  Maimonides Medical Center

  PRINCIPAL INVESTIGATOR

• Karan Wats, MBBS

  Maimonides Medical Center

  PRINCIPAL INVESTIGATOR

• Syeda A Batul, MBBS

  Maimonides Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Departmental head , Division of Heart Failure

Study Record Dates

• First Submitted: October 29, 2015
• First Posted: December 31, 2015
• Study Start: March 1, 2016
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: August 10, 2018

Record last verified: 2018-03

Locations

US (1)