NCT01975064

Brief Summary

The purpose of this study is to determine whether anesthesia maintained with propofol results in better one- and five-year-survival than anesthesia maintained with sevoflurane.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5,774

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2013

Longer than P75 for phase_4

Geographic Reach
3 countries

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 28, 2013

Completed
4 days until next milestone

Study Start

First participant enrolled

November 1, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 4, 2013

Completed
8.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2022

Completed
Last Updated

December 14, 2022

Status Verified

December 1, 2022

Enrollment Period

8.8 years

First QC Date

October 28, 2013

Last Update Submit

December 12, 2022

Conditions

Breast NeoplasmsColonic NeoplasmsRectal Neoplasms

Keywords

Breast neoplasmsColonic neoplasmsRectal neoplasms

Outcome Measures

Primary Outcomes (1)

  • Over all survival

    Measured from day of surgical procedure to day of death or day of censoring

    Five years

Secondary Outcomes (1)

  • Over all survival

    One year

Study Arms (2)

Propofol

ACTIVE COMPARATOR

Propofol for maintenance of anesthesia

Drug: Propofol

Sevoflurane

ACTIVE COMPARATOR

Sevoflurane for maintenance of anesthesia

Drug: Sevoflurane

Interventions

PropofolDRUG

Propofol will be infused individually for a sufficient level of anesthesia during the entire surgical procedure.

Also known as: Diprivan, Propofol-Lipuro, Propolipid
Propofol
SevofluraneDRUG

Sevoflurane will be administered by vaporizer individually for a sufficient level of anesthesia during the entire surgical procedure.

Also known as: Sevoflurane Baxter, Sevorane inhalation vapour
Sevoflurane

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Be informed of the nature of the study and have provided written informed consent
  • At least 18 years of age
  • Patient that is scheduled for elective radical breast- or colorectal cancer surgery in general anesthesia. Radical surgery means that the aim of the surgery is to cure (adjuvant treatment such as chemotherapy and/or radiation therapy seen as part of the curative treatment).

You may not qualify if:

  • The surgery that is going to be made is an acute surgical procedure
  • The surgery that is going to be made is palliative surgery
  • Known or suspected hypersensitivity to either propofol or sevoflurane or presence of any contraindication according to the substances' valid summary of product characteristics.
  • Lack of suitability for participation in the trial, for any reason, as judged by the Investigator (e.g. communicative disturbances (language or intellectual)).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Peking University First Teaching Hospital

Beijing, 100034, China

Location

Shanghai Renji Hospital

Shanghai, China

Location

Fourth Military Medical University Hospital

Xijing, China

Location

Wroclaw Medical University

Wroclaw, 50-367, Poland

Location

County Hospital Helsingborg

Helsingborg, 25187, Sweden

Location

County Hospital, Kalmar

Kalmar, 39244, Sweden

Location

Linköping University Hospital

Linköping, 58185, Sweden

Location

Skane University Hospital, Lund

Lund, 22241, Sweden

Location

Örebro University Hospital

Örebro, 70185, Sweden

Location

Skellefteå Hospital

Skellefteå, 93141, Sweden

Location

County Hospital Sundsvall-Härnösand

Sundsvall, 85643, Sweden

Location

University Hospital, Uppsala

Uppsala, 75185, Sweden

Location

Växjö Hospital

Vaxjo, 35234, Sweden

Location

Västerås Hospital

Västerås, 72189, Sweden

Location

Center for Clinical Research

Västerås, SE-72189, Sweden

Location

Related Publications (26)

  • Arain MR, Buggy DJ. Anaesthesia for cancer patients. Curr Opin Anaesthesiol. 2007 Jun;20(3):247-53. doi: 10.1097/ACO.0b013e32814f1c34.

    PMID: 17479030RESULT

  • Brand JM, Kirchner H, Poppe C, Schmucker P. The effects of general anesthesia on human peripheral immune cell distribution and cytokine production. Clin Immunol Immunopathol. 1997 May;83(2):190-4. doi: 10.1006/clin.1997.4351.

    PMID: 9143381RESULT

  • Braz MG, Magalhaes MR, Salvadori DM, Ferreira AL, Braz LG, Sakai E, Braz JR. Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery. Eur J Anaesthesiol. 2009 Aug;26(8):654-60. doi: 10.1097/eja.0b013e328329b12c.

    PMID: 19593899RESULT

  • Deegan CA, Murray D, Doran P, Ecimovic P, Moriarty DC, Buggy DJ. Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro. Br J Anaesth. 2009 Nov;103(5):685-90. doi: 10.1093/bja/aep261. Epub 2009 Sep 22.

    PMID: 19776028RESULT

  • Deegan CA, Murray D, Doran P, Moriarty DC, Sessler DI, Mascha E, Kavanagh BP, Buggy DJ. Anesthetic technique and the cytokine and matrix metalloproteinase response to primary breast cancer surgery. Reg Anesth Pain Med. 2010 Nov-Dec;35(6):490-5. doi: 10.1097/AAP.0b013e3181ef4d05.

    PMID: 20975461RESULT

  • Gilliland HE, Armstrong MA, Carabine U, McMurray TJ. The choice of anesthetic maintenance technique influences the antiinflammatory cytokine response to abdominal surgery. Anesth Analg. 1997 Dec;85(6):1394-8. doi: 10.1097/00000539-199712000-00039.

    PMID: 9390615RESULT

  • Gordon RJ. Anesthesia dogmas and shibboleths: barriers to patient safety? Anesth Analg. 2012 Mar;114(3):694-9. doi: 10.1213/ANE.0b013e3182455b86. No abstract available.

    PMID: 22358052RESULT

  • Graziola E, Elena G, Gobbo M, Mendez F, Colucci D, Puig N. [Stress, hemodynamic and immunological responses to inhaled and intravenous anesthetic techniques for video-assisted laparoscopic cholecystectomy]. Rev Esp Anestesiol Reanim. 2005 Apr;52(4):208-16. Spanish.

    PMID: 15901026RESULT

  • Hoerauf KH, Wiesner G, Schroegendorfer KF, Jobst BP, Spacek A, Harth M, Sator-Katzenschlager S, Rudiger HW. Waste anaesthetic gases induce sister chromatid exchanges in lymphocytes of operating room personnel. Br J Anaesth. 1999 May;82(5):764-6. doi: 10.1093/bja/82.5.764.

    PMID: 10536559RESULT

  • Inada T, Kubo K, Kambara T, Shingu K. Propofol inhibits cyclo-oxygenase activity in human monocytic THP-1 cells. Can J Anaesth. 2009 Mar;56(3):222-9. doi: 10.1007/s12630-008-9035-0. Epub 2009 Jan 28.

    PMID: 19247743RESULT

  • Inada T, Yamanouchi Y, Jomura S, Sakamoto S, Takahashi M, Kambara T, Shingu K. Effect of propofol and isoflurane anaesthesia on the immune response to surgery. Anaesthesia. 2004 Oct;59(10):954-9. doi: 10.1111/j.1365-2044.2004.03837.x.

    PMID: 15488052RESULT

  • Ji FH, Wang YL, Yang JP. Effects of propofol anesthesia and sevoflurane anesthesia on the differentiation of human T-helper cells during surgery. Chin Med J (Engl). 2011 Feb;124(4):525-9.

    PMID: 21362275RESULT

  • Ke JJ, Zhan J, Feng XB, Wu Y, Rao Y, Wang YL. A comparison of the effect of total intravenous anaesthesia with propofol and remifentanil and inhalational anaesthesia with isoflurane on the release of pro- and anti-inflammatory cytokines in patients undergoing open cholecystectomy. Anaesth Intensive Care. 2008 Jan;36(1):74-8. doi: 10.1177/0310057X0803600113.

    PMID: 18326136RESULT

  • Krause TK, Jansen L, Scholz J, Bottcher H, Wappler F, Burmeister MA, am Esch JS. Propofol anesthesia in children does not induce sister chromatid exchanges in lymphocytes. Mutat Res. 2003 Dec 9;542(1-2):59-64. doi: 10.1016/j.mrgentox.2003.08.007.

    PMID: 14644354RESULT

  • Kurosawa S, Kato M. Anesthetics, immune cells, and immune responses. J Anesth. 2008;22(3):263-77. doi: 10.1007/s00540-008-0626-2. Epub 2008 Aug 7.

    PMID: 18685933RESULT

  • Kushida A, Inada T, Shingu K. Enhancement of antitumor immunity after propofol treatment in mice. Immunopharmacol Immunotoxicol. 2007;29(3-4):477-86. doi: 10.1080/08923970701675085.

    PMID: 18075859RESULT

  • Looney M, Doran P, Buggy DJ. Effect of anesthetic technique on serum vascular endothelial growth factor C and transforming growth factor beta in women undergoing anesthesia and surgery for breast cancer. Anesthesiology. 2010 Nov;113(5):1118-25. doi: 10.1097/ALN.0b013e3181f79a69.

    PMID: 20930611RESULT

  • Loop T, Dovi-Akue D, Frick M, Roesslein M, Egger L, Humar M, Hoetzel A, Schmidt R, Borner C, Pahl HL, Geiger KK, Pannen BH. Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro. Anesthesiology. 2005 Jun;102(6):1147-57. doi: 10.1097/00000542-200506000-00014.

    PMID: 15915027RESULT

  • Mammoto T, Mukai M, Mammoto A, Yamanaka Y, Hayashi Y, Mashimo T, Kishi Y, Nakamura H. Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett. 2002 Oct 28;184(2):165-70. doi: 10.1016/s0304-3835(02)00210-0.

    PMID: 12127688RESULT

  • Meiler SE. Long-term outcome after anesthesia and surgery: remarks on the biology of a newly emerging principle in perioperative care. Anesthesiol Clin. 2006 Jun;24(2):255-78. doi: 10.1016/j.atc.2006.03.002.

    PMID: 16927929RESULT

  • Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S. Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg. 2003 Nov;97(5):1331-1339. doi: 10.1213/01.ANE.0000082995.44040.07.

    PMID: 14570648RESULT

  • Schneemilch CE, Bank U. [Release of pro- and anti-inflammatory cytokines during different anesthesia procedures]. Anaesthesiol Reanim. 2001;26(1):4-10. German.

    PMID: 11256129RESULT

  • Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma D. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer. 2012 Mar 15;130(6):1237-50. doi: 10.1002/ijc.26448. Epub 2011 Nov 9.

    PMID: 21935924RESULT

  • Wiesner G, Schiewe-Langgartner F, Lindner R, Gruber M. Increased formation of sister chromatid exchanges, but not of micronuclei, in anaesthetists exposed to low levels of sevoflurane. Anaesthesia. 2008 Aug;63(8):861-4. doi: 10.1111/j.1365-2044.2008.05498.x. Epub 2008 Jun 6.

    PMID: 18540930RESULT

  • Enlund M, Berglund A, Enlund A, Lundberg J, Warnberg F, Wang DX, Ekman A, Ahlstrand R, Flisberg P, Hedlund L, Ostlund I, Bergkvist L; CAN-study group. Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane. EClinicalMedicine. 2023 Jun 9;60:102037. doi: 10.1016/j.eclinm.2023.102037. eCollection 2023 Jun.

    PMID: 37333664DERIVED

  • Enlund M, Enlund A, Berglund A, Bergkvist L. Rationale and Design of the CAN Study: an RCT of Survival after Propofol- or Sevoflurane-based Anesthesia for Cancer Surgery. Curr Pharm Des. 2019;25(28):3028-3033. doi: 10.2174/1381612825666190705184218.

    PMID: 31298158DERIVED

MeSH Terms

Conditions

Breast NeoplasmsColonic NeoplasmsRectal Neoplasms

Interventions

PropofolSevoflurane

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesColorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

PhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsMethyl EthersEthersHydrocarbons, FluorinatedHydrocarbons, Halogenated

Study Officials

  • Mats Enlund, M.D., Ph.D.

    Uppsala university, Center of Clinical Research, Vasteras, Sweden

    PRINCIPAL INVESTIGATOR

  • Leif Bergkvist, M.D., Ph.D.

    Uppsala university, Center of Clinical Research, Vasteras, Sweden

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 28, 2013

First Posted

November 4, 2013

Study Start

November 1, 2013

Primary Completion

August 31, 2022

Study Completion

August 31, 2022

Last Updated

December 14, 2022

Record last verified: 2022-12

Data Sharing

IPD Sharing
Will share

Anonymized individual patient data collected for this study can be made available on request via the corresponding author, taking into account possible legal restrictions (Swedish and EU; GDPR) and after presenting a sound proposal and ethics approval. A signed data access agreement is mandatory, including a description of the conditions for data release and the requirements for data transfer, storage, archiving, publication, and co-authorship. Also, study protocol, statistical analysis plan, informed consent form may be asked for. The time frame for data sharing is defined from six months after last publications of the result of each cancer local (breast, colon, rectum) up to three years thereafter.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
From six months after last publications of the result of each cancer localization (breast, colon, rectum) up to three years thereafter
Access Criteria
Legal restrictions (Swedish and EU; GDPR) taking into account and after presenting a sound proposal and ethics approval. A signed data access agreement is mandatory, including a description of the conditions for data release and the requirements for data transfer, storage, archiving, publication, and co-authorship.
More information

Locations

CN(3)PL(1)SE(11)