Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02213380
Other study ID # RAGA-Delirium
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date September 2014
Est. completion date January 2020

Study information

Verified date April 2024
Source Wenzhou Medical University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is evaluate postoperative delirium after general anesthesia and regional anesthesia in elderly patients undergoing hip fracture surgery. Our research hypotheses are: (1) regional anesthesia may contribute to decrease the incidence of postoperative delirium. (2) Regional anesthesia may improve the outcome of elderly patient and reduce healthcare costs associated with postoperative delirium. (3) Postoperative delirium may result in poor long-term functional outcomes.


Description:

Postoperative delirium (POD) is an acute confusional state associated with changes in consciousness, arousal level and cognitive status. Elderly patients with hip fractures have the high incidence of delirium. The high risk factor of delirium include: Age 65 years or older, cognitive impairment/dementia, current hip fracture, severe illness and so on. Many previous studies predict that the majority of general anesthetic and sedative agents can favour postoperative delirium. However, none of studies have investigated the effect of general anesthesia and the effect of regional anesthesia and general anesthesia on the postoperative delirium in elderly patients undergoing hip fracture surgery in China. This multicentre, prospective, randomized controlled clinical trial is designed to evaluate postoperative delirium after general anesthesia and regional anesthesia in elderly patients undergoing hip fracture surgery. Our research hypotheses are: (1) regional anesthesia may contribute to decrease the incidence of postoperative delirium. (2) Regional anesthesia may improve the outcome of elderly patient and reduce healthcare costs associated with postoperative delirium. (3) Postoperative delirium may result in poor long-term functional outcomes. This trial has the following nine investigational centers: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children hospital of Wenzhou Medical University, Wenzhou, China; Department of Anesthesiology, Tongji Hospital, Tongji Medical college, Huazhong University of Science & Technology, Wuhan, China; Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China; Department of Anesthesiology, Southwest Hospital, Chongqing, China; Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Anesthesiology, Beijing Jishuitan Hospital, Beijing, China; Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China; Department of Anesthesiology, The Second Hospital of Anhui Medical University, Anhui, China; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Eligible patients will be assigned into two study groups (group RA: regional anesthesia will be used, group GA: General anesthesia will be used) by centre-minimization randomization (web or telephone). There are 3 stratification factors: age (65-79,≥80), presence of delirium(yes, no), dementia(yes, no). There will be two teams of investigators involved in trial procedure and the patient's follow-up. Investigator A (experienced anesthetist), who are competent in caring for patients undergoing hip fracture surgery, will perform following works, which includes informed consent, randomization, anesthesia and recovery parameters. Investigator B will visit patient the day before surgery and 7days after surgery or until discharge to assess patient for presence, type and severity of delirium, collect other data during in hospital stay and follow up patients at 6 and 12 months. Investigator B will receive uniform training of using of CAM, Delirium Rating Scale-Revised-98 (DRS-R-98), MMSE and other test used in this trial) and will be not clear about protocol. Within 24 h before surgery, cognitive function of each patient will be assessed with the MMSE, the presence of delirium will be diagnosed with the CAM, the type and severity of delirium will be assessed with DRS-R-98 and the pain will be assessed with a 100-mm visual analog scale (VAS). Routine monitoring (NBP, continuous ECG, and pulse oximetry) was initiated on all patients. Premedication for anesthesia will be avoided before surgery. Any medication impairing cognitive function will not be recommended, if administered, must be recorded it in detail. Investigator A will allocated the patient into group GA or group RA according the centre-randomization with a unique registration number for each eligible patient. Treatment protocols for both groups will also stipulate no sedative be administrated during operation. Routine monitoring was initiated on all patients. Hypotension (Systolic Blood Pressure<90mmHg or drop of Mean Arterial Pressure>30%) should be treated with vasoactive agents or fluid boluses as deemed appropriate by anesthetists. Postoperative analgesia will be administered according to the local procedures of each clinical trial site, aiming to maintain a VAS pain score ≤ 30 mm. Both groups will receive routine postoperative care on orthopedic ward. All randomized patients will be followed up to 7 days after surgery (or discharge from the hospital). The 7 days follow-up includes: CAM, DRS-98-R (if applicable), VAS, Analgesic use (if applicable), Sedative use (if applicable), Post-operative morbidity and laboratory results (including serum hemoglobin, hematocrit, leucocytes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, serum creatinine and urea concentrations, serum sodium and potassium and serum glucose concentration). Concomitant medications, adverse events and serious adverse events are record in all study visits. Economic parameters include: time to be discharged from post operation, total cost in hospital and cost for anesthesia of patient. Investigator B will also assess patient with POD in clinic or at their residence at 6 and 12 months to assess for presence of delirium, its type and severity (CAM, DRS-98-R), cognitive function using MMSE, and quality of life using The MOS 36-item Short-Form Health Survey (SF-36) questionnaire. The study will be monitored regularly by the clinical research associate (CRA) through visits or telephone. CRA will verify the consistency of the data recorded on the case report forms with the source documents and the management of therapeutic batches, the presence and completeness of the investigator file.


Recruitment information / eligibility

Status Completed
Enrollment 950
Est. completion date January 2020
Est. primary completion date December 31, 2018
Accepts healthy volunteers No
Gender All
Age group 65 Years and older
Eligibility Inclusion Criteria: - older patient (=65 years) - patient with hip fracture and planned hip fracture surgery - patient willing to complete this study. Exclusion Criteria: - patient with multiple trauma or multiple fractures, pathological fractures, pelvic fractures, femur fractures - contraindication (serious illness or medical conditions) for general anesthesia - contraindication (infection at the site of needle insertion, coagulopathy, international normalized ratio >1.4, platelet count <80×109 litre-1, allergy to local anaesthetics and so on) for regional anesthesia; - patient who cannot complete the preoperative mental tests (CAM and/or Mini-Mental State Examination (MMSE)) of this clinical trial - patient known to susceptible to malignant hyperthermia - known allergy or hypersensitivity to any drugs administered during this clinical trial - previous participation in this clinical trial - participation in another clinical trial within 4 weeks prior to selection

Study Design


Intervention

Procedure:
method of anesthesia
General anesthesia and regional anesthesia. General anesthesia(general anesthesia combined with peripheral nerve blockade, general anesthesia combined with spinal/epidural anesthesia or single general anesthesia) will be used in group GA. Regional anesthesia(epidural, spinal, combined spinal and epidural anesthesia or nerve block) will be used in group RA

Locations

Country Name City State
China Beijing Jishuitan Hospital Beijing
China West China Hospital of Sichuan University Chengdu Sichuan
China Southwest Hospital Chongqing
China The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang
China The Second Hospital of Anhui Medical University Hefei Anhui
China The People's Hospital of Lishi Lishi Zhejiang
China The Central Hospital of Lishui City Lishui Zhejiang
China The First Affiliated Hospital of Nanchang University Nanchang Jiangxi
China Ningbo No.2 Hospital Ningbo Zhejiang
China Ningbo No.6 Hospital Ningbo Zhejiang
China Taizhou Hospital of Zhejiang Province Taizhou Zhejiang
China The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang
China Tongji Hospital, Tongji Medical college Wuhan Hubei

Sponsors (2)

Lead Sponsor Collaborator
Wenzhou Medical University National Research Institute for Family Planning, China

Country where clinical trial is conducted

China, 

References & Publications (23)

Abou-Setta AM, Beaupre LA, Rashiq S, Dryden DM, Hamm MP, Sadowski CA, Menon MR, Majumdar SR, Wilson DM, Karkhaneh M, Mousavi SS, Wong K, Tjosvold L, Jones CA. Comparative effectiveness of pain management interventions for hip fracture: a systematic review. Ann Intern Med. 2011 Aug 16;155(4):234-45. doi: 10.7326/0003-4819-155-4-201108160-00346. — View Citation

Bruce AJ, Ritchie CW, Blizard R, Lai R, Raven P. The incidence of delirium associated with orthopedic surgery: a meta-analytic review. Int Psychogeriatr. 2007 Apr;19(2):197-214. doi: 10.1017/S104161020600425X. Epub 2006 Sep 14. — View Citation

Cole MG. Persistent delirium in older hospital patients. Curr Opin Psychiatry. 2010 May;23(3):250-4. doi: 10.1097/YCO.0b013e32833861f6. — View Citation

Eeles EM, Hubbard RE, White SV, O'Mahony MS, Savva GM, Bayer AJ. Hospital use, institutionalisation and mortality associated with delirium. Age Ageing. 2010 Jul;39(4):470-5. doi: 10.1093/ageing/afq052. — View Citation

Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available. — View Citation

Fong TG, Jones RN, Shi P, Marcantonio ER, Yap L, Rudolph JL, Yang FM, Kiely DK, Inouye SK. Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009 May 5;72(18):1570-5. doi: 10.1212/WNL.0b013e3181a4129a. — View Citation

Furlaneto ME, Garcez-Leme LE. Delirium in elderly individuals with hip fracture: causes, incidence, prevalence, and risk factors. Clinics (Sao Paulo). 2006 Feb;61(1):35-40. doi: 10.1590/s1807-59322006000100007. Epub 2006 Mar 10. — View Citation

Huang MC, Lee CH, Lai YC, Kao YF, Lin HY, Chen CH. Chinese version of the Delirium Rating Scale-Revised-98: reliability and validity. Compr Psychiatry. 2009 Jan-Feb;50(1):81-5. doi: 10.1016/j.comppsych.2008.05.011. Epub 2008 Aug 23. — View Citation

Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990 Dec 15;113(12):941-8. doi: 10.7326/0003-4819-113-12-941. — View Citation

Kat MG, de Jonghe JF, Vreeswijk R, van der Ploeg T, van Gool WA, Eikelenboom P, Kalisvaart KJ. Mortality associated with delirium after hip-surgery: a 2-year follow-up study. Age Ageing. 2011 May;40(3):312-8. doi: 10.1093/ageing/afr014. Epub 2011 Mar 17. — View Citation

Kat MG, Vreeswijk R, de Jonghe JF, van der Ploeg T, van Gool WA, Eikelenboom P, Kalisvaart KJ. Long-term cognitive outcome of delirium in elderly hip surgery patients. A prospective matched controlled study over two and a half years. Dement Geriatr Cogn Disord. 2008;26(1):1-8. doi: 10.1159/000140611. Epub 2008 Jul 9. — View Citation

Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc. 2001 May;49(5):516-22. doi: 10.1046/j.1532-5415.2001.49108.x. — View Citation

McHorney CA, Ware JE Jr, Lu JF, Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care. 1994 Jan;32(1):40-66. doi: 10.1097/00005650-199401000-00004. — View Citation

Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. doi: 10.1016/s0140-6736(97)07382-0. Erratum In: Lancet 1998 Jun 6;351(9117):1742. — View Citation

Nie H, Zhao B, Zhang YQ, Jiang YH, Yang YX. Pain and cognitive dysfunction are the risk factors of delirium in elderly hip fracture Chinese patients. Arch Gerontol Geriatr. 2012 Mar-Apr;54(2):e172-4. doi: 10.1016/j.archger.2011.09.012. Epub 2011 Oct 19. — View Citation

Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Vila P, Jolles J, Papaioannou A, Abildstrom H, Silverstein JH, Bonal JA, Raeder J, Nielsen IK, Korttila K, Munoz L, Dodds C, Hanning CD, Moller JT; ISPOCD2(International Study of Postoperative Cognitive Dysfunction) Investigators. Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand. 2003 Mar;47(3):260-6. doi: 10.1034/j.1399-6576.2003.00057.x. — View Citation

Sanders RD, Pandharipande PP, Davidson AJ, Ma D, Maze M. Anticipating and managing postoperative delirium and cognitive decline in adults. BMJ. 2011 Jul 20;343:d4331. doi: 10.1136/bmj.d4331. No abstract available. — View Citation

Sanders RD. Hypothesis for the pathophysiology of delirium: role of baseline brain network connectivity and changes in inhibitory tone. Med Hypotheses. 2011 Jul;77(1):140-3. doi: 10.1016/j.mehy.2011.03.048. Epub 2011 Apr 16. — View Citation

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. Erratum In: Mayo Clin Proc. 2010 Apr;85(4):400. Dosage error in article text. — View Citation

Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001 Spring;13(2):229-42. doi: 10.1176/jnp.13.2.229. Erratum In: J Neuropsychiatry Clin Neurosci 2001 Summer;13(3):433. — View Citation

Witlox J, Slor CJ, Jansen RW, Kalisvaart KJ, van Stijn MF, Houdijk AP, Eikelenboom P, van Gool WA, de Jonghe JF. The neuropsychological sequelae of delirium in elderly patients with hip fracture three months after hospital discharge. Int Psychogeriatr. 2013 Sep;25(9):1521-31. doi: 10.1017/S1041610213000574. Epub 2013 May 7. — View Citation

Young J, Murthy L, Westby M, Akunne A, O'Mahony R; Guideline Development Group. Diagnosis, prevention, and management of delirium: summary of NICE guidance. BMJ. 2010 Jul 28;341:c3704. doi: 10.1136/bmj.c3704. No abstract available. — View Citation

Zakriya K, Sieber FE, Christmas C, Wenz JF Sr, Franckowiak S. Brief postoperative delirium in hip fracture patients affects functional outcome at three months. Anesth Analg. 2004 Jun;98(6):1798-1802. doi: 10.1213/01.ANE.0000117145.50236.90. — View Citation

* Note: There are 23 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants With Post-operative Delirium in 7 Days Post Operation Post-operative delirium diagnosed with Confusion Assessment Method in 7 days post operation
Secondary Number of Participants With Post-operative Delirium Number of participants with delirium includes patients who had delirium in the post in the first 7 post-operative days.
The severity of delirium was described using a severity score from 0 (no delirium) to 39 (highest severity) and subtypes of delirium as hyperactive, hypoactive or mixed.
within fist 7days post operation
Secondary Severity of Delirium The worst severity scores of delirium was diagnosed with the DRS-R-98 within 7 days within first 7days post operation
Secondary The Subtypes of Delirium Diagnosed in 7 Days Post Operation The subtypes of delirium diagnosed with the Delirium Rating Scale-Revised-98 (DRS-R-98).
Patients with the hyperactive subtype may be agitated, disoriented, and delusional, and may experience hallucinations. This presentation can be confused with that of schizophrenia, agitated dementia, or a psychotic disorder.
within first 7 days post operation
Secondary 30 Day Mortality Mortality within 30 days post operation 30 days after surgery
Secondary Acute Pain Score Using Visual Analogue Scale (VAS) The worst pain score within 7 days post-operation in both groups. The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between no pain(0 point) to worst pain (100 points). In 7days post operation
Secondary Length of Hospital Stay Length of hospital stay are measured from the anesthesia starting day to the discharge day till the day of discharge from hospital, an average of 7 days
Secondary Costs of Anesthetic Procedure Costs of anesthetic procedure only 1 day after operation
Secondary Total In-hospital Costs Entire expenditure in-hospital till the day of discharge
Secondary 6 Months Incidence of Delirium in clinic or at their residence, diagnosed with Confusion Assessment Method (CAM) 6 months after discharge
Secondary 12 Months Incidence of Delirium in clinic or at their residence, diagnosed with Confusion Assessment Method (CAM) 12 months after discharge
Secondary 6 Months Quality of Life using 36-Item Short Form Survey (SF-36) questionnaire 6 months after discharge
Secondary 12 Months Quality of Life using 36-Item Short Form Survey (SF-36) questionnaire 12months after discharge
See also
  Status Clinical Trial Phase
Recruiting NCT06355570 - Delirium After Cardiac Surgery in Intensive Care Units N/A
Recruiting NCT05242419 - A Study of Huperzine A Injection in Reducing Postoperative Delirium in Elderly Patients Undergoing Non-cardiac Surgery N/A
Recruiting NCT05765162 - Safe Brain Initiative, Operationalizing Precision Anaesthesia
Not yet recruiting NCT05949229 - The Effect of Preoperative Duloxetine on the Occurance of Postoperative Delirium in Patients Undergoing Cancer Surgery. Phase 1/Phase 2
Completed NCT04797052 - EEG Detection of Delirium N/A