NICardipine Neuroprotection in AortiC Surgery (NICNACS)

NCT00508118 | Terminated Phase 2 Results

• 1 other identifier: Pro00001612
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Objective The objective of this study is to discover whether an infusion of nicardipine is able to reduce the time taken to achieve electrocerebral silence (ECS) during cardiopulmonary bypass (CPB) for aortic surgery. Hypothesis By inhibiting cold-induced cerebral vasoconstriction, nicardipine will maintain cerebral blood flow and allow more rapid cooling of the brain during CPB. This will manifest as a reduction in the time taken to achieve ECS and also as a reduction in overall CPB time.

Conditions

Aortic Aneurysm, Thoracic

Keywords

Aortic Arch Reconstruction Surgery

Outcome Measures

Primary Outcomes (1)

• Duration From Initiation of Cardiopulmonary Bypass (CPB) to Electrocerebral Silence (ECS), Defined as no Discernable Electroencephalographic Activity at an Amplification of 2 Micro Volts (μV)/mm, Confirmed for 3 Minutes

  Day of surgery

Secondary Outcomes (7)

• Temperature at Which ECS Occurs

  Day of surgery through discharge

• Temperature at Which Ablation of(SSEP)Occurs

  Day of surgery through discharge

• Time Points of EEG Patterns

  Day of surgery through discharge

• Time Points for SSEP Latency and Amplitude Changes

  Day of surgery through discharge

• Bispectral Index Scores (BIS)

  Day of surgery through discharge

Study Arms (2)

1

EXPERIMENTAL

Nicardipine

Drug: Nicardipine

2

PLACEBO COMPARATOR

0.9% saline

Drug: 0.9% saline

Interventions

Nicardipine DRUG

on bypass

1

0.9% saline DRUG

on bypass

2

Eligibility Criteria

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

You may qualify if:

• All adult (\>18 years) patients at Duke University Medical Center (DUMC) presenting for elective aortic surgery scheduled to include a period of deep hypothermic circulatory arrest.

You may not qualify if:

• Failure to provide written informed consent
• Emergency operation
• Documented allergy to nicardipine

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (14)

• Guerit JM, Verhelst R, Rubay J, el Khoury G, Noirhomme P, Baele P, Dion R. The use of somatosensory evoked potentials to determine the optimal degree of hypothermia during circulatory arrest. J Card Surg. 1994 Sep;9(5):596-603. doi: 10.1111/j.1540-8191.1994.tb00892.x.

  PMID: 7994101 BACKGROUND

• Ghariani S, Liard L, Spaey J, Noirhomme PH, El Khoury GA, de Tourtchaninoff M, Dion RA, Guerit JM. Retrospective study of somatosensory evoked potential monitoring in deep hypothermic circulatory arrest. Ann Thorac Surg. 1999 Jun;67(6):1915-8; discussion 1919-21. doi: 10.1016/s0003-4975(99)00413-0.

  PMID: 10391338 BACKGROUND

• Fleck TM, Czerny M, Hutschala D, Koinig H, Wolner E, Grabenwoger M. The incidence of transient neurologic dysfunction after ascending aortic replacement with circulatory arrest. Ann Thorac Surg. 2003 Oct;76(4):1198-202. doi: 10.1016/s0003-4975(03)00832-4.

  PMID: 14530011 BACKGROUND

• Dahlbacka S, Makela J, Kaakinen T, Alaoja H, Heikkinen J, Laurila P, Kiviluoma K, Salomaki T, Tuominen H, Ohtonen P, Lepola P, Biancari F, Juvonen T. Propofol is associated with impaired brain metabolism during hypothermic circulatory arrest: an experimental microdialysis study. Heart Surg Forum. 2006;9(4):E710-8; discussion E718. doi: 10.1532/HSF98.20061022.

  PMID: 16844626 BACKGROUND

• Hirotani T, Kameda T, Kumamoto T, Shirota S. Aortic arch repair using hypothermic circulatory arrest technique associated with pharmacological brain protection. Eur J Cardiothorac Surg. 2000 Nov;18(5):545-9. doi: 10.1016/s1010-7940(00)00533-9.

  PMID: 11053815 BACKGROUND

• Khaladj N, Peterss S, Oetjen P, von Wasielewski R, Hauschild G, Karck M, Haverich A, Hagl C. Hypothermic circulatory arrest with moderate, deep or profound hypothermic selective antegrade cerebral perfusion: which temperature provides best brain protection? Eur J Cardiothorac Surg. 2006 Sep;30(3):492-8. doi: 10.1016/j.ejcts.2006.05.031. Epub 2006 Jul 20.

  PMID: 16857368 BACKGROUND

• Levy WJ, Pantin E, Mehta S, McGarvey M. Hypothermia and the approximate entropy of the electroencephalogram. Anesthesiology. 2003 Jan;98(1):53-7. doi: 10.1097/00000542-200301000-00012.

  PMID: 12502979 BACKGROUND

• Pokela M, Jantti V, Lepola P, Romsi P, Rimpilainen J, Kiviluoma K, Salomaki T, Vainionpaa V, Biancari F, Hirvonen J, Kaakinen T, Juvonen T. EEG burst recovery is predictive of brain injury after experimental hypothermic circulatory arrest. Scand Cardiovasc J. 2003 Jun;37(3):154-7. doi: 10.1080/14017430310006956.

  PMID: 12881157 BACKGROUND

• Puri GD, Bagchi A, Anandamurthy B, Dhaliwal RS. The Bispectral Index and induced hypothermia--electrocerebral silence at an unusually high temperature. Anaesth Intensive Care. 2003 Oct;31(5):578-80. doi: 10.1177/0310057X0303100515.

  PMID: 14601285 BACKGROUND

• Sakamoto T, Hatsuoka S, Stock UA, Duebener LF, Lidov HG, Holmes GL, Sperling JS, Munakata M, Laussen PC, Jonas RA. Prediction of safe duration of hypothermic circulatory arrest by near-infrared spectroscopy. J Thorac Cardiovasc Surg. 2001 Aug;122(2):339-50. doi: 10.1067/mtc.2001.115242.

  PMID: 11479508 BACKGROUND

• Speziali G, Russo P, Davis DA, Wagerle LC. Hypothermia enhances contractility in cerebral arteries of newborn lambs. J Surg Res. 1994 Jul;57(1):80-4. doi: 10.1006/jsre.1994.1114.

  PMID: 8041154 BACKGROUND

• Stecker MM, Cheung AT, Pochettino A, Kent GP, Patterson T, Weiss SJ, Bavaria JE. Deep hypothermic circulatory arrest: I. Effects of cooling on electroencephalogram and evoked potentials. Ann Thorac Surg. 2001 Jan;71(1):14-21. doi: 10.1016/s0003-4975(00)01592-7.

  PMID: 11216734 BACKGROUND

• Stecker MM, Cheung AT, Pochettino A, Kent GP, Patterson T, Weiss SJ, Bavaria JE. Deep hypothermic circulatory arrest: II. Changes in electroencephalogram and evoked potentials during rewarming. Ann Thorac Surg. 2001 Jan;71(1):22-8. doi: 10.1016/s0003-4975(00)02021-x.

  PMID: 11216751 BACKGROUND

• Stecker MM, Escherich A, Patterson T, Bavaria JE, Cheung AT. Effects of acute hypoxemia/ischemia on EEG and evoked responses at normothermia and hypothermia in humans. Med Sci Monit. 2002 Apr;8(4):CR223-8.

  PMID: 11951061 BACKGROUND

MeSH Terms

Conditions

Aortic Aneurysm, Thoracic

Interventions

Nicardipine; Saline Solution

Condition Hierarchy (Ancestors)

Aortic Aneurysm; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

This study was terminated early because of safety concerns in the active treatment group. In 3 patients randomized, the blind was broken in 3 because of refractory hypotension and acidosis requiring vasopressor therapy. All 3 were on active drug.

Results Point of Contact

• Title: Andrew Shaw MD
• Organization: Duke University Medical Center

andrew.shaw@duke.edu

919 286 6938

Study Officials

• Andy Shaw, M. D.

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2007
• First Posted: July 27, 2007
• Study Start: January 1, 2008
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: August 1, 2014
• Results First Posted: March 8, 2013

Record last verified: 2013-01

Locations

US (1)