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Postoperative Cognitive DysfunctionPhase 2NCT02848599

The Influence of Postoperative Analgesia on Systemic Inflammatory Response and POCD After Femoral Fractures Surgery

A Phase 2 study testing morphine and levobupivacaine in people with Postoperative Cognitive Dysfunction, run by Osijek University Hospital at 1 site in Croatia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine whether epidural levobupivacaine applied for the purpose of post-operative analgesia compared to systemic analgesia with morphine leads to better pain control, stronger suppression of the inflammatory response and the production of inflammatory mediators, faster recovery of… Read more about this study

Who is it for?
Ages 65 years and olderHealthy volunteers can take part
Conditions the study is for
Postoperative Cognitive Dysfunction
What is being tested?
morphine and levobupivacaine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
86 participants
Where
1 siteCroatia
Study dates
Jul 2016to Sep 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • patients age 65 and over
  • fracture of the proximal femur
  • preoperative assessment American Society of Anesthesiologists(ASA) score I - ASA III
  • a written consent of the patient to participate in research

Who cannot join

  • patient non-compliance
  • ASA status IV and IV above
  • patients younger than 65 years
  • dementia, Parkinson's disease, cerebrovascular accident history; simultaneous head injuries,the use of opioids and benzodiazepines longer than a month before the surgery; alcoholism; serious liver disease (class C according to Child-Pugh's classification); severe kidney disease that require dialysis
  • result of MMSE test (Mini-Mental State Examination) under 17
  • the existence of any contraindications for the implementation of regional anesthesia and one or other form of post-operative analgesia.

Trial locations and contacts

1 site in 1 country.

Croatia1 site
  • Clinical Hospital Centre Osijek

    Osijek, 31000

Other trials in Croatia

About this study

Official title: The Influence of Postoperative Analgesia on Systemic Inflammatory Response and Postoperative Cognitive Disfunction in Elderly Patients After Surgical Repair of Femoral Fractures

The purpose of this study is to determine whether epidural levobupivacaine applied for the purpose of post-operative analgesia compared to systemic analgesia with morphine leads to better pain control, stronger suppression of the inflammatory response and the production of inflammatory mediators, faster recovery of patients and consequently less incidence of postoperative cognitive dysfunction (POCD) in elderly patients after surgical treatment of femoral fractures.

Read the detailed description

The research will be carried out at the Department of Surgery at Clinical Hospital Centre(CHC) Osijek after approval by the Ethics Committee of CHC Osijek and will be organized as a prospective randomized trial. Respecting the including and excluding criteria for participation in the study, the research will include 70 patients aged 65 years and over who are undergoing surgery for proximal femur fractures and will be operated with the same operating technique (osteosynthesis with nail). All participants will receive the same type of anesthesia and one of two forms of post-operative analgesia, so it will be divided into two groups (35 patients) depending on which form of post-operative analgesia receive. Randomization will be performed by drawing an envelope in which the specified one or other form of post-operative analgesia will be written. The study will be stopped in case of serious complications life-threatening (excessive sedation, respiratory insufficiency, hemodynamic instability and profound hypotension, heart rhythm disorders), which could possibly be related to the administration of drugs used for postoperative analgesia.

Being tested
morphine, levobupivacaine
Keywords
postoperative analgesia, postoperative cognitive disfunction
Medical subject headings
Postoperative Cognitive Complications

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • morphineDrug

  • levobupivacaineDrug

    Also called Chirocaine

Study groups in NCT02848599
Study groupRoleWhat they receive
morphineActive comparatorThe patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
Receives: Drug: morphine
levobupivacaineActive comparatorUpon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
Receives: Drug: levobupivacaine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Interleukin-6 Concentration in Peripheral Blood.

    Measurement will be done before and 24 and 72 hours after the surgery.

    Measured: Before, 24 and 72 hours after the surgery

  2. Changes in Cognitive Function

    Assessment of cognitive function will be done using the Mini-mental state examination (MMSE) rating scales before and 24,48,72,96 and 120 hours after the surgery at the same time every morning.

    Mini-Mental State Examination Scale: minimum score is 0 and maximum score is 30; the severity of cognitive impairment: no cognitive impairment=25-30; mild cognitive impairment=19-24; moderate cognitive impairment=10-18; and severe cognitive impairment<9. Higher scores mean a better and lower scores mean a worse outcome.

    Measured: Before, 24,48,72,96 and 120 hours after the surgery

Secondary outcomes (4)
  1. Changes in C-reactive Protein (CRP) Levels

    Measurement will be done before and 24,72 and 120 hours after the surgery.

    Measured: Before, 24,72 and 120 hours after the surgery

  2. Changes in Fibrinogen Concentrations in Peripheral Blood

    Measurement will be done before and 24,72 and 120 hours after the surgery.

    Measured: Before, 24,72 and 120 hours after the surgery

  3. Changes in Pain Intensity

    Assessment will be done using Numeric Rating Scale (NRS). During the first 72 hours after the surgery assessment will be done every 3 hours, after that assessment will be done 3 times daily. Median of 8 time points measurements during the first 24, 48 and 72 hours after the surgery will be reported. After that, median of 3 time points will be reported from the 4. to 6. postoperative day and on the day of discharge.

    Minimum score 0 and maximum score 10 ( 0-No Pain; 1-3 Mild Pain; 4-6 Moderate Pain; 7-10 Severe Pain ). Higher scores mean a worse and lower scores mean a better outcome.

    Measured: During the first 72 hours after the surgery assessment will be done every 3 hours, after that assessment will be done 3 times daily until discharge

  4. Postoperative Hospital Stay

    Duration of postoperative hospital stay in days

    Measured: 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2016 (estimated)
  2. Study startJul 2016
  3. Primary completionJul 2017
  4. Study completionSep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02848599
Sponsor's protocol ID
25-1:6563-3/2014
Status last verified
Aug 2020
First submitted
20 Jul 2016
Last updated
1 Sep 2020
Data monitoring committee
No
Individual data sharing
No

Publications

  • Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010 Jul 28;304(4):443-51. doi: 10.1001/jama.2010.1013.

    PubMed 20664045
  • Raats JW, van Eijsden WA, Crolla RM, Steyerberg EW, van der Laan L. Risk Factors and Outcomes for Postoperative Delirium after Major Surgery in Elderly Patients. PLoS One. 2015 Aug 20;10(8):e0136071. doi: 10.1371/journal.pone.0136071. eCollection 2015.

    PubMed 26291459
  • Wang W, Wang Y, Wu H, Lei L, Xu S, Shen X, Guo X, Shen R, Xia X, Liu Y, Wang F. Postoperative cognitive dysfunction: current developments in mechanism and prevention. Med Sci Monit. 2014 Oct 12;20:1908-12. doi: 10.12659/MSM.892485.

    PubMed 25306127
  • Vega P E, Nazar J C, Rattalino F M, Pedemonte T J, Carrasco G M. [Postoperative delirium among older people]. Rev Med Chil. 2014 Apr;142(4):481-93. doi: 10.4067/S0034-98872014000400010. Spanish.

    PubMed 25117039
  • Vacas S, Degos V, Feng X, Maze M. The neuroinflammatory response of postoperative cognitive decline. Br Med Bull. 2013;106(1):161-78. doi: 10.1093/bmb/ldt006. Epub 2013 Apr 4.

    PubMed 23558082
  • Zywiel MG, Prabhu A, Perruccio AV, Gandhi R. The influence of anesthesia and pain management on cognitive dysfunction after joint arthroplasty: a systematic review. Clin Orthop Relat Res. 2014 May;472(5):1453-66. doi: 10.1007/s11999-013-3363-2.

    PubMed 24186470
  • Kampe S, Weinreich G, Darr C, Eicker K, Stamatis G, Hachenberg T. The impact of epidural analgesia compared to systemic opioid-based analgesia with regard to length of hospital stay and recovery of bowel function: retrospective evaluation of 1555 patients undergoing thoracotomy. J Cardiothorac Surg. 2014 Nov 23;9:175. doi: 10.1186/s13019-014-0175-8.

    PubMed 25417134
  • Popping DM, Elia N, Van Aken HK, Marret E, Schug SA, Kranke P, Wenk M, Tramer MR. Impact of epidural analgesia on mortality and morbidity after surgery: systematic review and meta-analysis of randomized controlled trials. Ann Surg. 2014 Jun;259(6):1056-67. doi: 10.1097/SLA.0000000000000237.

    PubMed 24096762
  • Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923.

    PubMed 22762316
  • Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008 Jan 14;168(1):27-32. doi: 10.1001/archinternmed.2007.4.

    PubMed 18195192
  • McDaniel M, Brudney C. Postoperative delirium: etiology and management. Curr Opin Crit Care. 2012 Aug;18(4):372-6. doi: 10.1097/MCC.0b013e3283557211.

    PubMed 22732435
  • Hansen MV. Chronobiology, cognitive function and depressive symptoms in surgical patients. Dan Med J. 2014 Sep;61(9):B4914.

    PubMed 25186550
  • Seitz DP, Adunuri N, Gill SS, Rochon PA. Prevalence of dementia and cognitive impairment among older adults with hip fractures. J Am Med Dir Assoc. 2011 Oct;12(8):556-564. doi: 10.1016/j.jamda.2010.12.001. Epub 2011 Mar 8.

    PubMed 21450227
  • Sieber FE, Zakriya KJ, Gottschalk A, Blute MR, Lee HB, Rosenberg PB, Mears SC. Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clin Proc. 2010 Jan;85(1):18-26. doi: 10.4065/mcp.2009.0469.

    PubMed 20042557
  • van Harten AE, Scheeren TW, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia. 2012 Mar;67(3):280-93. doi: 10.1111/j.1365-2044.2011.07008.x.

    PubMed 22321085

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing morphine and levobupivacaine in people with Postoperative Cognitive Dysfunction, run by Osijek University Hospital at 1 site in Croatia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Interleukin-6 Concentration in Peripheral Blood. (time frame: Before, 24 and 72 hours after the surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02848599, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2020.

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