- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02213380
Effect of Anesthesia on Post-operative Delirium in Elderly Patients Undergoing Hip Fracture Surgery (RAGADelirium)
Effect of Regional Anaesthesia and General Anaesthesia on Postoperative Delirium in Elderly Patients Undergoing Hip Fracture Surgery: a Multicenter Randomized Controlled Trial.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Beijing, China, 100000
- BeiJing JiShuiTan Hospital
-
Chongqing, China, 400038
- Southwest Hospital
-
-
Anhui
-
Hefei, Anhui, China, 230601
- The Second Hospital of Anhui Medical University
-
-
Hubei
-
Wuhan, Hubei, China, 430030
- Tongji Hospital, Tongji Medical College
-
-
Jiangxi
-
Nanchang, Jiangxi, China, 330006
- The First Affiliated Hospital of NanChang University
-
-
Sichuan
-
Chengdu, Sichuan, China, 610041
- West China Hospital of Sichuan University
-
-
Zhejiang
-
Hangzhou, Zhejiang, China, 310000
- The Second Affiliated Hospital of Zhejiang University School of Medicine
-
Lishi, Zhejiang, China, 323000
- The People's Hospital of Lishi
-
Lishui, Zhejiang, China, 323000
- The Central Hospital of Lishui City
-
Ningbo, Zhejiang, China, 315010
- Ningbo No.2 Hospital
-
Ningbo, Zhejiang, China, 315040
- Ningbo No.6 Hospital
-
Taizhou, Zhejiang, China, 317000
- Taizhou Hospital of Zhejiang Province
-
Wenzhou, Zhejiang, China, 325000
- The First Affiliated Hospital of Wenzhou Medical University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: group GA
General 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 |
Other: group RA
Regional 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 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Post-operative Delirium in 7 Days Post Operation
Time Frame: in 7 days post operation
|
Post-operative delirium diagnosed with Confusion Assessment Method
|
in 7 days post operation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Post-operative Delirium
Time Frame: within fist 7days post operation
|
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
|
Severity of Delirium
Time Frame: within first 7days post operation
|
The worst severity scores of delirium was diagnosed with the DRS-R-98 within 7 days
|
within first 7days post operation
|
The Subtypes of Delirium Diagnosed in 7 Days Post Operation
Time Frame: within first 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
|
30 Day Mortality
Time Frame: 30 days after surgery
|
Mortality within 30 days post operation
|
30 days after surgery
|
Acute Pain Score Using Visual Analogue Scale (VAS)
Time Frame: In 7days post operation
|
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
|
Length of Hospital Stay
Time Frame: till the day of discharge from hospital, an average of 7 days
|
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
|
Costs of Anesthetic Procedure
Time Frame: 1 day after operation
|
Costs of anesthetic procedure only
|
1 day after operation
|
Total In-hospital Costs
Time Frame: till the day of discharge
|
Entire expenditure in-hospital
|
till the day of discharge
|
6 Months Incidence of Delirium
Time Frame: 6 months after discharge
|
in clinic or at their residence, diagnosed with Confusion Assessment Method (CAM)
|
6 months after discharge
|
12 Months Incidence of Delirium
Time Frame: 12 months after discharge
|
in clinic or at their residence, diagnosed with Confusion Assessment Method (CAM)
|
12 months after discharge
|
6 Months Quality of Life
Time Frame: 6 months after discharge
|
using 36-Item Short Form Survey (SF-36) questionnaire
|
6 months after discharge
|
12 Months Quality of Life
Time Frame: 12months after discharge
|
using 36-Item Short Form Survey (SF-36) questionnaire
|
12months after discharge
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Fang Gao, M.D., The Second Affiliated Hospital & Yuying Children hospital of Wenzhou Medical University
- Study Director: Jun Li, M.D., The Second Affiliated Hospital & Yuying Children hospital of Wenzhou Medical University
- Study Director: Joice Yeung, M.D., Heart of England NHS Foundation Trust
- Study Director: Teresa Moledy, Heart of England NHS Foundation Trust
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Cole MG. Persistent delirium in older hospital patients. Curr Opin Psychiatry. 2010 May;23(3):250-4. doi: 10.1097/YCO.0b013e32833861f6.
- 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.
- 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.
- 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.
- Li T, Li J, Yuan L, Wu J, Jiang C, Daniels J, Mehta RL, Wang M, Yeung J, Jackson T, Melody T, Jin S, Yao Y, Wu J, Chen J, Smith FG, Lian Q; RAGA Study Investigators. Effect of Regional vs General Anesthesia on Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery: The RAGA Randomized Trial. JAMA. 2022 Jan 4;327(1):50-58. doi: 10.1001/jama.2021.22647. Erratum In: JAMA. 2022 Mar 22;327(12):1188.
- Li T, Yeung J, Li J, Zhang Y, Melody T, Gao Y, Wang Y, Lian Q, Gao F; RAGA-Delirium Investigators. Comparison of regional with general anaesthesia on postoperative delirium (RAGA-delirium) in the older patients undergoing hip fracture surgery: study protocol for a multicentre randomised controlled trial. BMJ Open. 2017 Oct 22;7(10):e016937. doi: 10.1136/bmjopen-2017-016937.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Neurologic Manifestations
- Fractures, Bone
- Wounds and Injuries
- Confusion
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Leg Injuries
- Femoral Fractures
- Hip Injuries
- Delirium
- Hip Fractures
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Anesthetics
Other Study ID Numbers
- RAGA-Delirium
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Post Operative Delirium
-
Mayo ClinicCompletedPost-Operative DeliriumUnited States
-
Amira Hassan Ahmed AliNot yet recruitingPost Operative DeliriumEgypt
-
Imperial College Healthcare NHS TrustRecruitingCardiac Surgery | Intensive Care Unit Delirium | Post Operative DeliriumUnited Kingdom
-
Oregon Health and Science UniversityRecruitingNeurocognitive Disorders | Anesthesia | Post-operative Cognitive Dysfunction | Post-operative DeliriumUnited States
-
Charite University, Berlin, GermanyCompletedPost-operative Cognitive Dysfunction | Post-operative DeliriumGermany
-
Albert Einstein College of MedicineNational Institute on Aging (NIA)CompletedPost-operative Delirium | Post-operative Cognitive DeclineUnited States
-
University of PadovaRecruitingEmergence Delirium | Post-Operative Cognitive DysfunctionItaly
-
Charite University, Berlin, GermanyTerminatedDelirium and Post-operative Cognitive Dysfunction (POCD)Germany
-
University of PadovaMaran EleonoraUnknownEmergence Delirium | Post-Operative Cognitive Dysfunction
-
Menoufia UniversityCompleted
Clinical Trials on method of anesthesia
-
Seoul National University HospitalRecruiting
-
University of North Carolina, Chapel HillWithdrawn
-
University of PennsylvaniaEmory University; American Heart AssociationRecruitingCardiovascular DiseasesUnited States
-
Istanbul UniversityRecruitingAmelogenesis Imperfecta | Dental Age EstimationTurkey
-
Pirogov Russian National Research Medical UniversityCompletedCarotid Stenosis | Carotid Artery DiseasesRussian Federation
-
Federal University of BahiaCompletedStroke | Cerebrovascular DisordersBrazil
-
Sunnybrook Health Sciences CentreCanadian Institutes of Health Research (CIHR)Completed
-
Firat UniversityNot yet recruitingPain | Child Development | Nursing CareTurkey
-
JSI Research & Training Institute, Inc.UnknownWasting | Severe Acute Malnutrition
-
Dr. Behcet Uz Children's HospitalRecruitingAcute Respiratory Distress Syndrome | Acute Respiratory Failure | Pediatric Acute Respiratory Distress Syndrome (PARDS)Turkey