Anesthesiological Strategies in Elective Craniotomy

NCT00741351 | Completed Phase 3 DMC

• 2 other identifiers: EudraCT number 2007-005279-32AIFA FARM6FKJKK
• Study Type: interventional
• Target: 411
• Locations: 1 country
• Sites: 15

Brief Summary

This protocol, NeuroMorfeo, aims to assess equivalence between volatile and intravenous anesthetics for neurosurgical procedures.

Conditions

Anesthesia; Craniotomy; Neurosurgery

Keywords

Anesthesia; Craniotomy; Neurosurgery

Outcome Measures

Primary Outcomes (1)

• Post-anesthesia awaking time, assessed as the interval (min:sec)required to reach an ALDRETE score ≥ 9

  From estubation to aldrete score ≥ 9

Secondary Outcomes (5)

• Neurovegetative stress

  From induction of anesthesia to 24 hours after surgery

• Intraoperative and post-operative adverse events assessment

  From induction of anesthesia to 24 hours after surgery

• Brain relaxation evaluated by a blinded neurosurgeon

  From induction of anesthesia to 24 hours after surgery

• Patient's satisfaction

  From induction of anesthesia to 24 hours after surgery

• Costs of the three strategies

  From induction of anesthesia to end of surgery

Study Arms (3)

IF

EXPERIMENTAL

Sevoflurane (Inhalation)+Fentanyl

Drug: Sevoflurane + Fentanyl

IR

EXPERIMENTAL

Sevoflurane (Inhalation)+Remifentanyl

Drug: Sevoflurane + Remifentanyl

ER

EXPERIMENTAL

Propofol (Endovenous)+ Remifentanyl

Drug: Propofol + Remifentanyl

Interventions

Sevoflurane + Fentanyl DRUG

Sevoflurane is maintained in a MAC range (0.75% to 1.25%) and fentanyl (2-3 microg/kg/hr or 0.7 microg/kg boluses). Just before incision of the scalp, fentanyl (1-2microg/kg/hr) can be supplemented, if necessary

IF

Sevoflurane + Remifentanyl DRUG

Sevoflurane is maintained in a MAC range (0.75% to 1.25%) and remifentanil (0.5-0.25 microg/kg/min reduced to 0.05-0.1 microg/kg/min after dural opening). Just before incision of the scalp, remifentanil can be supplemented, if necessary

IR

Propofol + Remifentanyl DRUG

Propofol is maintained with continuous infusion at 10 mg/kg/h for the first 10 minutes, then reduced to 8 mg/kg/h for the following 10 minutes and reduced to 6mg/kg/h thereafter and remifentanil 0.5-0.25 microg/kg/min reduced to 0.05-0.1 microg/kg/min after dural opening. Just before incision of the scalp, remifentanil could be supplemented, if necessary

ER

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient scheduled for elective intracranial surgery under general anesthesia for a supratentorial mass lesion in the next 24 hours;
• Physical state, evaluated with the ASA (American Society of Anesthesiologists ) classification I (normal healthy patient), II (patient with mild systemic disease), or III (patient with severe systemic disease);
• Age 18-75 years;
• Normal preoperative level of consciousness, i.e. Glasgow Coma Scale (GCS) = 15;
• No signs of intracranial hypertension.

You may not qualify if:

• Severe cardiovascular pathology, as uncontrolled arterial hypertension, documented reduced coronary reserve.
• Renal or liver disease precluding the use of either anesthetic technique.
• Pregnancy .
• Known allergies to any anesthetic agent.
• Reduced preoperative level of consciousness, i.e.
• Glasgow Coma Scale (GCS) \< 15.
• Body weight greater than 120 kg.
• History of drug abuse or psychiatric conditions.
• Documented disturbance of the hypothalamic region.Refusal to sign consent form.
• Participation in other clinical trials.
• Delayed awakening, because, due to the location or size of the lesion, postoperative sedation and mechanical ventilation are planned.

Sponsors & Collaborators

• Azienda Ospedaliera San Gerardo di Monza: lead

Study Sites (15)

Policlinico Consorziale di Bari

Bari, Italy

Location

Ospedale Bellaria Bologna

Bologna, 40100, Italy

Location

IRCCS Fondazione San Raffaele Milano

Milan, 20100, Italy

Location

Istituto di Ricerche Farmacologiche Mario Negri - Dipartimento di Ricerca Cardiovascolare-

Milan, 20100, Italy

Location

Azienda Ospedaliera San Gerardo

Monza, 20052, Italy

Location

Ospedale Maggiore della Carità di Novara

Novara, 28100, Italy

Location

Ospedale di Padova

Padua, 35128, Italy

Location

Azienda Ospedaliera di Parma

Parma, 43100, Italy

Location

Policlinico "A. Gemelli" Roma

Rome, Italy

Location

Policlinico "Umberto I" Roma

Rome, Italy

Location

Azienda Universitaria Senese

Siena, 53100, Italy

Location

Ospedale San Giovanni Bosco Torino

Turin, 10057, Italy

Location

Ospedale San giovanni Battista Torino

Turin, Italy

Location

Ospedale di Circolo e Fondazione Macchi Varese

Varese, 21100, Italy

Location

Azienda Ospedaliera Universitaria di Verona

Verona, 37121, Italy

Location

Related Publications (26)

• Hans P, Bonhomme V. Why we still use intravenous drugs as the basic regimen for neurosurgical anaesthesia. Curr Opin Anaesthesiol. 2006 Oct;19(5):498-503. doi: 10.1097/01.aco.0000245274.69292.ad.

  PMID: 16960481 BACKGROUND

• Todd MM, Warner DS, Sokoll MD, Maktabi MA, Hindman BJ, Scamman FL, Kirschner J. A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy. Propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide. Anesthesiology. 1993 Jun;78(6):1005-20. doi: 10.1097/00000542-199306000-00002.

  PMID: 8512094 BACKGROUND

• Engelhard K, Werner C. Inhalational or intravenous anesthetics for craniotomies? Pro inhalational. Curr Opin Anaesthesiol. 2006 Oct;19(5):504-8. doi: 10.1097/01.aco.0000245275.76916.87.

  PMID: 16960482 BACKGROUND

• Magni G, Baisi F, La Rosa I, Imperiale C, Fabbrini V, Pennacchiotti ML, Rosa G. No difference in emergence time and early cognitive function between sevoflurane-fentanyl and propofol-remifentanil in patients undergoing craniotomy for supratentorial intracranial surgery. J Neurosurg Anesthesiol. 2005 Jul;17(3):134-8. doi: 10.1097/01.ana.0000167447.33969.16.

  PMID: 16037733 BACKGROUND

• Talke P, Caldwell JE, Brown R, Dodson B, Howley J, Richardson CA. A comparison of three anesthetic techniques in patients undergoing craniotomy for supratentorial intracranial surgery. Anesth Analg. 2002 Aug;95(2):430-5, table of contents. doi: 10.1097/00000539-200208000-00036.

  PMID: 12145066 BACKGROUND

• Gomberg-Maitland M, Frison L, Halperin JL. Active-control clinical trials to establish equivalence or noninferiority: methodological and statistical concepts linked to quality. Am Heart J. 2003 Sep;146(3):398-403. doi: 10.1016/S0002-8703(03)00324-7.

  PMID: 12947355 BACKGROUND

• Aldrete JA. The post-anesthesia recovery score revisited. J Clin Anesth. 1995 Feb;7(1):89-91. doi: 10.1016/0952-8180(94)00001-k. No abstract available.

  PMID: 7772368 BACKGROUND

• Balakrishnan G, Raudzens P, Samra SK, Song K, Boening JA, Bosek V, Jamerson BD, Warner DS. A comparison of remifentanil and fentanyl in patients undergoing surgery for intracranial mass lesions. Anesth Analg. 2000 Jul;91(1):163-9. doi: 10.1097/00000539-200007000-00030.

  PMID: 10866905 BACKGROUND

• Del Gaudio A, Ciritella P, Perrotta F, Puopolo M, Lauta E, Mastronardi P, De Vivo P. Remifentanil vs fentanyl with a target controlled propofol infusion in patients undergoing craniotomy for supratentorial lesions. Minerva Anestesiol. 2006 May;72(5):309-19. English, Italian.

  PMID: 16675939 BACKGROUND

• Klingstedt C, Giesecke K, Hamberger B, Jarnberg PO. High- and low-dose fentanyl anaesthesia: circulatory and plasma catecholamine responses during cholecystectomy. Br J Anaesth. 1987 Feb;59(2):184-8. doi: 10.1093/bja/59.2.184.

  PMID: 3828169 BACKGROUND

• Nishiyama T, Yamashita K, Yokoyama T. Stress hormone changes in general anesthesia of long duration: isoflurane-nitrous oxide vs sevoflurane-nitrous oxide anesthesia. J Clin Anesth. 2005 Dec;17(8):586-91. doi: 10.1016/j.jclinane.2005.03.009.

  PMID: 16427527 BACKGROUND

• Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000 Jul;85(1):109-17. doi: 10.1093/bja/85.1.109. No abstract available.

  PMID: 10927999 BACKGROUND

• Bent JM, Paterson JL, Mashiter K, Hall GM. Effects of high-dose fentanyl anaesthesia on the established metabolic and endocrine response to surgery. Anaesthesia. 1984 Jan;39(1):19-23. doi: 10.1111/j.1365-2044.1984.tb09447.x.

  PMID: 6696213 BACKGROUND

• Heesen M, Deinsberger W, Dietrich GV, Detsch O, Boldt J, Hempelmann G. Increase of interleukin-6 plasma levels after elective craniotomy: influence of interleukin-10 and catecholamines. Acta Neurochir (Wien). 1996;138(1):77-80. doi: 10.1007/BF01411728.

  PMID: 8686529 BACKGROUND

• Ledowski T, Bein B, Hanss R, Paris A, Fudickar W, Scholz J, Tonner PH. Neuroendocrine stress response and heart rate variability: a comparison of total intravenous versus balanced anesthesia. Anesth Analg. 2005 Dec;101(6):1700-1705. doi: 10.1213/01.ane.0000184041.32175.14.

  PMID: 16301244 BACKGROUND

• Guzzetti S, Borroni E, Garbelli PE, Ceriani E, Della Bella P, Montano N, Cogliati C, Somers VK, Malliani A, Porta A. Symbolic dynamics of heart rate variability: a probe to investigate cardiac autonomic modulation. Circulation. 2005 Jul 26;112(4):465-70. doi: 10.1161/CIRCULATIONAHA.104.518449. Epub 2005 Jul 18.

  PMID: 16027252 BACKGROUND

• Olsen KS, Pedersen CB, Madsen JB, Ravn LI, Schifter S. Vasoactive modulators during and after craniotomy: relation to postoperative hypertension. J Neurosurg Anesthesiol. 2002 Jul;14(3):171-9. doi: 10.1097/00008506-200207000-00001.

  PMID: 12172288 BACKGROUND

• Leslie K, Troedel S. Does anaesthesia care affect the outcome following craniotomy? J Clin Neurosci. 2002 May;9(3):231-6. doi: 10.1054/jocn.2001.0934. No abstract available.

  PMID: 12093125 BACKGROUND

• Hall GM, Young C, Holdcroft A, Alaghband-Zadeh J. Substrate mobilisation during surgery. A comparison between halothane and fentanyl anaesthesia. Anaesthesia. 1978 Nov-Dec;33(10):924-30.

  PMID: 727414 BACKGROUND

• Fung D, Cohen M, Stewart S, Davies A. Can the Iowa Satisfaction with Anesthesia Scale be used to measure patient satisfaction with cataract care under topical local anesthesia and monitored sedation at a community hospital? Anesth Analg. 2005 Jun;100(6):1637-1643. doi: 10.1213/01.ANE.0000154203.00434.23.

  PMID: 15920188 BACKGROUND

• Citerio G, Stocchetti N, Cormio M, Beretta L. Neuro-Link, a computer-assisted database for head injury in intensive care. Acta Neurochir (Wien). 2000;142(7):769-76. doi: 10.1007/s007010070091.

  PMID: 10955671 BACKGROUND

• Piper I, Citerio G, Chambers I, Contant C, Enblad P, Fiddes H, Howells T, Kiening K, Nilsson P, Yau YH; BrainIT Group. The BrainIT group: concept and core dataset definition. Acta Neurochir (Wien). 2003 Aug;145(8):615-28; discussion 628-9. doi: 10.1007/s00701-003-0066-6.

  PMID: 14520540 BACKGROUND

• Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ; CONSORT Group. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA. 2006 Mar 8;295(10):1152-60. doi: 10.1001/jama.295.10.1152.

  PMID: 16522836 BACKGROUND

• Le Henanff A, Giraudeau B, Baron G, Ravaud P. Quality of reporting of noninferiority and equivalence randomized trials. JAMA. 2006 Mar 8;295(10):1147-51. doi: 10.1001/jama.295.10.1147.

  PMID: 16522835 BACKGROUND

• Kaul S, Diamond GA. Good enough: a primer on the analysis and interpretation of noninferiority trials. Ann Intern Med. 2006 Jul 4;145(1):62-9. doi: 10.7326/0003-4819-145-1-200607040-00011.

  PMID: 16818930 BACKGROUND

• Citerio G, Franzosi MG, Latini R, Masson S, Barlera S, Guzzetti S, Pesenti A. Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial--the NeuroMorfeo trial. Trials. 2009 Apr 6;10:19. doi: 10.1186/1745-6215-10-19.

  PMID: 19348675 DERIVED

MeSH Terms

Interventions

Sevoflurane; Fentanyl; Remifentanil; Propofol

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propionates; Acids, Acyclic; Carboxylic Acids; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Giuseppe Citerio, MD

  Azienda Ospedaliera San Gerardo Monza

  PRINCIPAL INVESTIGATOR

• Antonio Pesenti, MD

  Università delgi Studi Milano Bicocca

  STUDY CHAIR

• Maria Grazia Franzosi, PhD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY CHAIR

• Roberto Latini, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 22, 2008
• First Posted: August 26, 2008
• Study Start: December 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: December 1, 2009
• Last Updated: September 8, 2011

Record last verified: 2011-09

Locations

IT (15)