Neuromorfeo: Anesthesiological Strategies in Elective Craniotomy

Sponsor

Azienda Ospedaliera San Gerardo di Monza (Other)

Overall Status

Completed

CT.gov ID

NCT00741351

Collaborator

(none)

411

Enrollment

Locations

Arms

Duration (Months)

27.4

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Anesthesia Craniotomy Neurosurgery	Drug: Sevoflurane + Fentanyl Drug: Sevoflurane + Remifentanyl Drug: Propofol + Remifentanyl	Phase 3

Detailed Description

NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for a elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state evaluated with the ASA (I-III) and Glasgow Coma Scale (GCS) equal to 15, will be randomly assigned to one of three anesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanesthesia will be evaluated by comparing the intervals required to reach, after anesthesia discontinuation, a modified Aldrete score ≥ 9 (primary end-point). Two statistical comparisons have been planned: 1) sevoflurane + fentanyl vs. propofol + remifentanil; 2) sevoflurane + remifentanil vs. propofol + remifentanil.

Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anesthesia; intraoperative adverse events (i.e. hypotension, hypertension, requirement of osmotic agents or/and hyperventilation for controlling brain swelling); evaluation of surgical field; postoperative adverse events (as seizures, cough, shivering, agitation, postoperative hematoma and postoperative pain); patient's satisfaction and an analysis of costs.

411 patients will be recruited in 14 different Italian centers during an 18-month period.

The recruitment started December 20th, 2007 and up to 11th March 2009.

Study Design

Study Type:

Interventional

Actual Enrollment :

411 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Anesthesiological Strategies in Elective Craniotomy: Randomized, Equivalence, Open Trial

Study Start Date :

Dec 1, 2007

Actual Primary Completion Date :

Mar 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IF Sevoflurane (Inhalation)+Fentanyl	Drug: Sevoflurane + Fentanyl 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
Experimental: IR Sevoflurane (Inhalation)+Remifentanyl	Drug: Sevoflurane + Remifentanyl 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
Experimental: ER Propofol (Endovenous)+ Remifentanyl	Drug: Propofol + Remifentanyl 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

Arm

Intervention/Treatment

Experimental: IF

Sevoflurane (Inhalation)+Fentanyl

Drug: Sevoflurane + Fentanyl

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

Experimental: IR

Sevoflurane (Inhalation)+Remifentanyl

Drug: Sevoflurane + Remifentanyl

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

Experimental: ER

Propofol (Endovenous)+ Remifentanyl

Drug: Propofol + Remifentanyl

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

Outcome Measures

Primary Outcome Measures

Post-anesthesia awaking time, assessed as the interval (min:sec)required to reach an ALDRETE score ≥ 9 [From estubation to aldrete score ≥ 9]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

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.

Exclusion criteria:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Policlinico Consorziale di Bari	Bari	Italy
2	Ospedale Bellaria Bologna	Bologna	Italy	40100
3	IRCCS Fondazione San Raffaele Milano	Milan	Italy	20100
4	Istituto di Ricerche Farmacologiche Mario Negri - Dipartimento di Ricerca Cardiovascolare-	Milan	Italy	20100
5	Azienda Ospedaliera San Gerardo	Monza	Italy	20052
6	Ospedale Maggiore della Carità di Novara	Novara	Italy	28100
7	Ospedale di Padova	Padua	Italy	35128
8	Azienda Ospedaliera di Parma	Parma	Italy	43100
9	Policlinico "A. Gemelli" Roma	Rome	Italy
10	Policlinico "Umberto I" Roma	Rome	Italy
11	Azienda Universitaria Senese	Siena	Italy	53100
12	Ospedale San Giovanni Bosco Torino	Turin	Italy	10057
13	Ospedale San giovanni Battista Torino	Turin	Italy
14	Ospedale di Circolo e Fondazione Macchi Varese	Varese	Italy	21100
15	Azienda Ospedaliera Universitaria di Verona	Verona	Italy	37121

Sponsors and Collaborators

Azienda Ospedaliera San Gerardo di Monza

Investigators

Principal Investigator: Giuseppe Citerio, MD, Azienda Ospedaliera San Gerardo Monza
Study Chair: 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