Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan Surgery

NCT00543309 | Terminated Phase 2 Results DMC

• 1 other identifier: 0735070N
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

The staged surgical pathway to treat children with single ventricle heart defects culminates with the Fontan operation. In this procedure, systemic venous return is rerouted directly to the pulmonary arteries, which serves to separate the systemic and pulmonary circulations. Although mortality following the Fontan operation is now uncommon, early postoperative morbidity including prolonged postoperative chest tube drainage and hospitalization remains significant. The efficacy of empiric inotropic, vasodilator and neurohumoral-inhibitory therapies in the perioperative period is unknown and practice varies widely between centers. The investigators will propose a single-center, randomized, double-blind, phase II clinical trial in children undergoing Fontan surgery. The investigators plan to compare the effects of perioperative nesiritide, milrinone and placebo infusions on the early postoperative clinical course and neurohumoral profile. The investigators hypothesize that, when compared to the milrinone and placebo groups, the nesiritide group will have more days alive and out of the hospital within the first 30 days after surgery.

Conditions

Heart Defects, Congenital

Keywords

Fontan Operation; Cardiopulmonary Bypass; Heart Defects, Congenital; Milrinone; Natriuretic peptide, brain

Outcome Measures

Primary Outcomes (1)

• Days Alive and Out of the Hospital Within 30 Days of Surgery.

  30 days

Secondary Outcomes (14)

• Cardiovascular: Cardiac Index

  Postoperative hour #1

• Cardiovascular: Cardiac Index

  Postoperative hour #8

• Cardiovascular: Arrhythmia

  Postoperative day (POD) #0 through 5

• Cardiovascular: Peak Inotrope Score

  Initial 24 hours in CICU

• Cardiovascular: Peak Lactate Level

  Initial 24 hours in CICU

Study Arms (3)

I- nesiritide

EXPERIMENTAL

Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met.

Drug: nesiritide

II- Milrinone

ACTIVE COMPARATOR

Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met.

Drug: milrinone

III- placebo

PLACEBO COMPARATOR

Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met.

Drug: placebo

Interventions

nesiritide DRUG

Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted

Also known as: Natrecor

I- nesiritide

milrinone DRUG

Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted

Also known as: Primacor

II- Milrinone

placebo DRUG

Placebo bolus on CPB, then placebo infusion

III- placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing an elective, primary Fontan operation at Children's Hospital Boston.

You may not qualify if:

• Revision surgery for failing Fontan circulation.
• Preoperative serum creatinine \> 1.5 mg/dL or chronic dialysis.
• The attending surgeon, cardiac anesthesiologist, or cardiac intensivist has a compelling indication to initiate either nesiritide or milrinone outside of the confines of the study.

Sponsors & Collaborators

• John M Costello: lead
• American Heart Association: collaborator

Study Sites (1)

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Costello JM, Dunbar-Masterson C, Allan CK, Gauvreau K, Newburger JW, McGowan FX Jr, Wessel DL, Mayer JE Jr, Salvin JW, Dionne RE, Laussen PC. Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial. Circ Heart Fail. 2014 Jul;7(4):596-604. doi: 10.1161/CIRCHEARTFAILURE.113.001312. Epub 2014 Jun 6.

  PMID: 24906491 RESULT

MeSH Terms

Conditions

Heart Defects, Congenital

Interventions

Natriuretic Peptide, Brain; Milrinone

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Natriuretic Peptides; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Amrinone; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Single center design limits generalizability of findings. Study drug doses were extrapolated from published experience in other patient types. Study may have been underpowered to detect differences among treatment groups for secondary outcomes.

Results Point of Contact

• Title: John M. Costello, M.D., M.P.H.
• Organization: Ann & Robert H. Lurie Children's Hospital of Chicago

jmcostello@luriechildrens.org

312 227 1551

Study Officials

• John M Costello, MD MPH

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate in Cardiology

Study Record Dates

• First Submitted: October 10, 2007
• First Posted: October 12, 2007
• Study Start: October 1, 2007
• Primary Completion: January 1, 2013
• Study Completion: July 1, 2013
• Last Updated: June 25, 2018
• Results First Posted: June 25, 2018

Record last verified: 2018-05

Locations

US (1)