The Influence of Beta Blocker Therapy on the Hemodynamic Response to Inotrope Infusion in Patients With Acute Decompensated Heart Failure

NCT01971944 | Completed

• 1 other identifier: 11-1985
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: To compare the hemodynamic effects of dobutamine and milrinone in hospitalized patients who are receiving Beta Blocker Participants: Patients who are admitted to the General Cardiology and Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure, who have maintained steady state concentrations of beta blocker therapy (carvedilol or metoprolol), and who are deemed by the health care team to require pulmonary artery catheter placement and inotropic therapy with dobutamine or milrinone by continuous infusion. Patients that are not currently receiving beta blocker therapy will be enrolled for comparative purposes; however, any patient not at steady state (on or off beta blocker therapy) will not be enrolled. Procedures: After obtaining informed consent, patients will be assigned to the appropriate sub-study group based on beta blocker use (Study A: patients on stable doses of metoprolol and Study B: patients on stable doses of carvedilol). All patients should receive dobutamine followed by milrinone as outlined in the dosing algorithm (see inotrope dosing algorithm attached, as part of the usual standard of practice). Baseline pulmonary artery catheter hemodynamic parameters will be collected prior to administration of inotrope trial of dobutamine followed by milrinone. Hemodynamic parameters will be recorded per the dosing algorithm following initiation and dose titration. Dose titration will be determined by the health care team based upon patient response or lack thereof and tolerability. Changes in hemodynamic parameters in response to dobutamine or milrinone will be compared within study groups. Additionally, data will continue to be collected on patients receiving not beta blocker therapy for comparative purpose.

Conditions

Acute Decompensated Heart Failure; Heart Failure

Keywords

Beta Blocker; Inotrope

Outcome Measures

Primary Outcomes (1)

• Change in Fick Cardiac Index ( Fick CI) from baseline to maximum tolerated dose of inotrope therapy

  Dobutamine will be titrated every 2 hours as tolerated for a total of 3 titrations. Data will be collected over the 6 hour infusion. Milrinone titration timeframes are dependent on renal function and as tolerated by patients. A total of 3 titrations may occur as tolerated over incremental timeframes of 4, 12, 18 and 24 hours. Data will be collected over the 12-72 hours the patient will be receiving the milrinone infusion.

  baseline to maximum tolerated dose. (up to 6 hours)

Study Arms (3)

Patients achieving steady state concentrations of carvedilol

Patients achieving steady state concentrations of carvedilol who receive a trial of dobutamine followed by milrinone.

Patients achieving steady state concentrations of metoprolol

Patients achieving steady state concentrations of metoprolol who receive a trial of dobutamine followed by milrinone.

Patients not receiving beta blocker

Patients not receiving beta blocker who receive a trial of dobutamine followed by milrinone.

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who are admitted to the General Cardiology and Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure, and who are deemed by the health care team to require pulmonary artery catheter placement and inotropic therapy with either dobutamine or milrinone by continuous infusion.

You may qualify if:

• Patients ≥ 18 years of age and English-speaking who are admitted to the General Cardiology or Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure (ADHF).
• Patients deemed by the health care team to require hemodynamic monitoring with a pulmonary artery catheter and inotropic therapy. Patients receiving at least 3 doses of continued beta blocker therapy with carvedilol, metoprolol succinate, or metoprolol tartrate and patients receiving no beta blocker therapy or have missed at least 5 doses of beta-blocker therapy.

You may not qualify if:

• Concomitant treatment with other beta blockers, non-selective alpha blockers (e.g. terazosin, prazosin, doxazosin), non-dihydropyridine calcium antagonists, antiarrhythmic agents except for chronic stables doses of amiodarone, dofetilide or mexiletine.
• Use of inotropes or IV vasoactive agents within 7 days or at time of enrollment Patients with hemodynamically unstable arrhythmias (e.g., Systolic Blood Pressure (SBP) \< 80, Heart Rate (HR) \> 110), uncorrected primary valvular disease, or current mechanical support including left ventricular assist device (LVADs), Impella devices and balloon pumps
• Patients who have missed more than 1 dose of beta blocker within 72 hours of starting inotrope
• No subjects will be excluded based upon race, gender or ethnicity.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

UNC Healthcare

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (4)

• Bollano E, Tang MS, Hjalmarson A, Waagstein F, Andersson B. Different responses to dobutamine in the presence of carvedilol or metoprolol in patients with chronic heart failure. Heart. 2003 Jun;89(6):621-4. doi: 10.1136/heart.89.6.621.

  PMID: 12748215 BACKGROUND

• Metra M, Nodari S, D'Aloia A, Muneretto C, Robertson AD, Bristow MR, Dei Cas L. Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: a randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol. J Am Coll Cardiol. 2002 Oct 2;40(7):1248-58. doi: 10.1016/s0735-1097(02)02134-4.

  PMID: 12383572 BACKGROUND

• Lowes BD, Tsvetkova T, Eichhorn EJ, Gilbert EM, Bristow MR. Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol. Int J Cardiol. 2001 Dec;81(2-3):141-9. doi: 10.1016/s0167-5273(01)00520-4.

  PMID: 11744130 BACKGROUND

• Woolfrey SG, Hegbrant J, Thysell H, Fox PA, Lendrem DW, Lockwood GF, Lasher K, Rogers J, Greenslade D. Dose regimen adjustment for milrinone in congestive heart failure patients with moderate and severe renal failure. J Pharm Pharmacol. 1995 Aug;47(8):651-5. doi: 10.1111/j.2042-7158.1995.tb05853.x.

  PMID: 8583366 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Jo Ellen Rodgers, PharmD

  UNC Healthcare

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2013
• First Posted: October 30, 2013
• Study Start: December 1, 2010
• Primary Completion: September 1, 2017
• Study Completion: October 1, 2018
• Last Updated: November 14, 2018

Record last verified: 2018-11

Locations

US (1)