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Dexmedetomidine Supplemented Analgesia and Delirium After Hip Fracture Surgery

Primary Purpose

Elderly, Hip Fracture Surgery, Patient-controlled Analgesia

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Dexmedetomidine
Placebo
Sponsored by
Peking University First Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Elderly focused on measuring Elderly, Hip fracture surgery, Patient-controlled analgesia, Dexmedetomidine, Postoperative delirium

Eligibility Criteria

65 Years - 89 Years (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 65 years but < 90 years;
  • Scheduled to undergo hip fracture surgery;
  • Planned to use patient-controlled intravenous analgesia (PCIA) after surgery.

Exclusion Criteria:

  • Refuse to participate in this study;
  • Preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis;
  • Inability to communicate in the preoperative period because of coma, profound dementia or language barrier;
  • Preoperative obstructive sleep apnea (diagnosed sleep apnea syndrome or a STOP-Bang score ≥3 combined with a serum bicarbonate ≥28 mmol/L);
  • Sick sinus syndrome, severe sinus bradycardia (< 50 beats per minute), or second-degree or above atrioventricular block without pacemaker;
  • Severe hepatic dysfunction (Child-Pugh class C);
  • Severe renal dysfunction (requirement of renal replacement therapy before surgery);
  • American Society of Anesthesiologists physical status >IV, or estimated survival ≤24 h.

Sites / Locations

  • Peking University First HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dexmedetomidine group

Control group

Arm Description

Patients in this group receive dexmedetomidine-supplemented patient-controlled analgesia for up to 3 days after surgery. The formula is a mixture of dexmedetomidine (1 microgram/ml) and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is programmed to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes.

Patients in this group receive routine patient-controlled analgesia for up to 3 days after surgery. The formula is a mixture of placebo and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is programmed to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes.

Outcomes

Primary Outcome Measures

Incidence of delirium within the first 5 days after surgery
Delirium is assessed twice daily (8:00-10:00 am, 18:00-20:00 pm) with the 3-minute Diagnostic Confusion Assessment Method (3D CAM, for patients without mechanical ventilation) or the Confusion Assessment Method for the intensive care unit (CAM-ICU, for patients with mechanical ventilation) during postoperative days 1-5.

Secondary Outcome Measures

Daily prevalence of delirium during the first 5 days after surgery
Delirium is assessed twice daily (8:00-10:00 am, 18:00-20:00 pm) with the 3-minute Diagnostic Confusion Assessment Method (3D CAM, for patients without mechanical ventilation) or the Confusion Assessment Method for the intensive care unit (CAM-ICU, for patients with mechanical ventilation) during postoperative days 1-5.
Length of stay in hospital after surgery
Length of stay in hospital after surgery
Incidence of non-delirium complications within 30 days after surgery
Non-delirium complications are defined as new-onset medical events other than delirium that are harmful to patients' recovery and required therapeutic intervention, i.e., grade II or above on the Clavien-Dindo classification.
All-cause 30-day mortality
All-cause 30-day mortality
Quality of life at 30 days
Quality of life is assessed with the WHOQOL-BREF, a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function.
Cognitive function at 30 days
Cognitive function is assessed with the TICS-m, a 12-item questionnaire that provides an assessment of global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function.
Overall survival for up to 3 years after surgery
Time from surgery to all-cause death
Event-free survival for up to 3 years after surgery
Time from surgery to new-onset diseases or all-cause death, whichever comes first. New-onset disease indicates those that required hospital admission and/or interventional procedures.
Quality of life in 1-,2- and 3-year survivors after surgery
Quality of life is assessed with the WHOQOL-BREF, a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function.
Cognitive function in 1-,2- and 3-year survivors after surgery
Cognitive function is assessed with the TICS-m, a 12-item questionnaire that provides an assessment of global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function.

Full Information

First Posted
July 4, 2021
Last Updated
November 25, 2021
Sponsor
Peking University First Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04955249
Brief Title
Dexmedetomidine Supplemented Analgesia and Delirium After Hip Fracture Surgery
Official Title
Impact of Dexmedetomidine Supplemented Analgesia on Delirium and Long-term Outcomes in Elderly After Hip Fracture Surgery: A Multicenter, Double-blinded, Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
November 18, 2021 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University First Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Delirium is common in the elderly after hip fracture surgery, and is associated with worse outcomes. The investigators hypothesize that, for elderly patients after hip fracture surgery, dexmedetomidine supplemented analgesia can reduce the incidence of delirium and improve the long-term outcomes.
Detailed Description
Delirium is a common complication in patients after hip fracture surgery and is associated with worse outcomes, including prolonged hospital stay, poor functional recovery, decreased cognitive function, increased health care costs, and elevated mortality rate. The etiology of delirium is multifactorial and include severe pain and sleep disturbances after surgery, as well as surgery-related inflammation. Dexmedetomidine is a selective alpha 2 receptor agonist. It exerts sedative effects by activating the endogenous sleep-promoting pathway and leads to a state like non-rapid eye movement sleep. It produces analgesic effects by activating the alpha2a adrenergic receptor subtype in the spinal cord. Perioperative dexmedetomidine also alleviates the degree of surgery-related inflammation. Previous studies showed that, for elderly patients admitted to the intensive care unit after non-cardiac surgery, low-dose dexmedetomidine infusion improved subjective sleep quality and reduced delirium early after surgery; it also increased survival up to 2 years and improved life quality in 3-year survivors. The investigators hypothesize that dexmedetomidine supplemented patient-controlled analgesia can also reduce delirium and improve long-term outcomes in elderly patients after hip fracture surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Elderly, Hip Fracture Surgery, Patient-controlled Analgesia, Dexmedetomidine, Postoperative Delirium
Keywords
Elderly, Hip fracture surgery, Patient-controlled analgesia, Dexmedetomidine, Postoperative delirium

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1440 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dexmedetomidine group
Arm Type
Experimental
Arm Description
Patients in this group receive dexmedetomidine-supplemented patient-controlled analgesia for up to 3 days after surgery. The formula is a mixture of dexmedetomidine (1 microgram/ml) and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is programmed to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes.
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Patients in this group receive routine patient-controlled analgesia for up to 3 days after surgery. The formula is a mixture of placebo and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is programmed to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes.
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Other Intervention Name(s)
Intervention group
Intervention Description
Patients in this group receive dexmedetomidine-supplemented patient-controlled analgesia for up to 3 days after surgery. The formula is a mixture of dexmedetomidine (1 microgram/ml) and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is programmed to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Control group
Intervention Description
Patients in this group receive routine patient-controlled intravenous analgesia for up to 3 days after surgery. The formula is a mixture of placebo and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes.
Primary Outcome Measure Information:
Title
Incidence of delirium within the first 5 days after surgery
Description
Delirium is assessed twice daily (8:00-10:00 am, 18:00-20:00 pm) with the 3-minute Diagnostic Confusion Assessment Method (3D CAM, for patients without mechanical ventilation) or the Confusion Assessment Method for the intensive care unit (CAM-ICU, for patients with mechanical ventilation) during postoperative days 1-5.
Time Frame
Up to 5 days after surgery
Secondary Outcome Measure Information:
Title
Daily prevalence of delirium during the first 5 days after surgery
Description
Delirium is assessed twice daily (8:00-10:00 am, 18:00-20:00 pm) with the 3-minute Diagnostic Confusion Assessment Method (3D CAM, for patients without mechanical ventilation) or the Confusion Assessment Method for the intensive care unit (CAM-ICU, for patients with mechanical ventilation) during postoperative days 1-5.
Time Frame
Up to 5 days after surgery
Title
Length of stay in hospital after surgery
Description
Length of stay in hospital after surgery
Time Frame
Up to 30 days after surgery
Title
Incidence of non-delirium complications within 30 days after surgery
Description
Non-delirium complications are defined as new-onset medical events other than delirium that are harmful to patients' recovery and required therapeutic intervention, i.e., grade II or above on the Clavien-Dindo classification.
Time Frame
Up to 30 days after surgery
Title
All-cause 30-day mortality
Description
All-cause 30-day mortality
Time Frame
Up to 30 days after surgery
Title
Quality of life at 30 days
Description
Quality of life is assessed with the WHOQOL-BREF, a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function.
Time Frame
At the 30th day after surgery
Title
Cognitive function at 30 days
Description
Cognitive function is assessed with the TICS-m, a 12-item questionnaire that provides an assessment of global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function.
Time Frame
At the 30th day after surgery
Title
Overall survival for up to 3 years after surgery
Description
Time from surgery to all-cause death
Time Frame
Up to 3 years after surgery
Title
Event-free survival for up to 3 years after surgery
Description
Time from surgery to new-onset diseases or all-cause death, whichever comes first. New-onset disease indicates those that required hospital admission and/or interventional procedures.
Time Frame
Up to 3 years after surgery
Title
Quality of life in 1-,2- and 3-year survivors after surgery
Description
Quality of life is assessed with the WHOQOL-BREF, a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function.
Time Frame
At the end of the 1st, 2nd, and 3rd year after surgery
Title
Cognitive function in 1-,2- and 3-year survivors after surgery
Description
Cognitive function is assessed with the TICS-m, a 12-item questionnaire that provides an assessment of global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function.
Time Frame
At the end of the 1st, 2nd, and 3rd year after surgery
Other Pre-specified Outcome Measures:
Title
Cumulative sufentanil consumption within 5 postoperative days
Description
Cumulative sufentanil consumption within 5 postoperative days
Time Frame
Up to 5 days after surgery
Title
Pain severity during postoperative days 1-5
Description
Pain severity is assessed with twice daily the Numeric Rating Scale (NRS), an 11 point scale where 0=no pain and 10=the worst possible pain.
Time Frame
Up to 5 days after surgery
Title
Subjective sleep quality during postoperative days 1-5
Description
Subjective sleep quality is assessed once daily with the Numeric Rating Scale (NRS), an 11 point scale where 0=the best sleep and 10=the worst sleep.
Time Frame
Up to 5 days after surgery
Title
Sedation level during postoperative days 1-5
Description
Sedation level is assessed twice daily with the Richmond Agitation-Sedation Scale (RASS), of which the range is as follows: +4 (combative), +3 (very agitated), +2 (agitated), +1 (restless), 0 (alert and clam), -1 (drowsy), -2 (light sedation), -3 (moderate sedation), -4 (deep sedation), and -5 (unarousable).
Time Frame
Up to 5 days after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 65 years but < 90 years; Scheduled to undergo hip fracture surgery; Planned to use patient-controlled intravenous analgesia (PCIA) after surgery. Exclusion Criteria: Refuse to participate in this study; Preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis; Inability to communicate in the preoperative period because of coma, profound dementia or language barrier; Preoperative obstructive sleep apnea (diagnosed sleep apnea syndrome or a STOP-Bang score ≥3 combined with a serum bicarbonate ≥28 mmol/L); Sick sinus syndrome, severe sinus bradycardia (< 50 beats per minute), or second-degree or above atrioventricular block without pacemaker; Severe hepatic dysfunction (Child-Pugh class C); Severe renal dysfunction (requirement of renal replacement therapy before surgery); American Society of Anesthesiologists physical status >IV, or estimated survival ≤24 h.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dong-Xin Wang
Phone
8610 83572784
Email
wangdongxin@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hong Hong
Phone
861083572460
Email
honghong920066@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dong-Xin Wang, MD, PhD
Organizational Affiliation
Study Principal Investigator
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University First Hospital
City
Beijing
ZIP/Postal Code
100034
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dong-Xin Wang, MD, PhD
Phone
8610 83572784
Email
wangdongxin@hotmail.com
First Name & Middle Initial & Last Name & Degree
Hong Hong, MD
Phone
8610 83572460
Email
honghong920066@sina.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26873816
Citation
Yang Y, Zhao X, Dong T, Yang Z, Zhang Q, Zhang Y. Risk factors for postoperative delirium following hip fracture repair in elderly patients: a systematic review and meta-analysis. Aging Clin Exp Res. 2017 Apr;29(2):115-126. doi: 10.1007/s40520-016-0541-6. Epub 2016 Feb 12.
Results Reference
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PubMed Identifier
30229446
Citation
Malik AT, Quatman CE, Phieffer LS, Ly TV, Khan SN. Incidence, risk factors and clinical impact of postoperative delirium following open reduction and internal fixation (ORIF) for hip fractures: an analysis of 7859 patients from the ACS-NSQIP hip fracture procedure targeted database. Eur J Orthop Surg Traumatol. 2019 Feb;29(2):435-446. doi: 10.1007/s00590-018-2308-6. Epub 2018 Sep 18.
Results Reference
background
PubMed Identifier
14729554
Citation
Cole MG. Delirium in elderly patients. Am J Geriatr Psychiatry. 2004 Jan-Feb;12(1):7-21.
Results Reference
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PubMed Identifier
28525512
Citation
Mu DL, Zhang DZ, Wang DX, Wang G, Li CJ, Meng ZT, Li YW, Liu C, Li XY. Parecoxib Supplementation to Morphine Analgesia Decreases Incidence of Delirium in Elderly Patients After Hip or Knee Replacement Surgery: A Randomized Controlled Trial. Anesth Analg. 2017 Jun;124(6):1992-2000. doi: 10.1213/ANE.0000000000002095.
Results Reference
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PubMed Identifier
16181163
Citation
Kalisvaart KJ, de Jonghe JF, Bogaards MJ, Vreeswijk R, Egberts TC, Burger BJ, Eikelenboom P, van Gool WA. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. 2005 Oct;53(10):1658-66. doi: 10.1111/j.1532-5415.2005.53503.x.
Results Reference
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PubMed Identifier
27542303
Citation
Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16.
Results Reference
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PubMed Identifier
29661417
Citation
Weinstein SM, Poultsides L, Baaklini LR, Morwald EE, Cozowicz C, Saleh JN, Arrington MB, Poeran J, Zubizarreta N, Memtsoudis SG. Postoperative delirium in total knee and hip arthroplasty patients: a study of perioperative modifiable risk factors. Br J Anaesth. 2018 May;120(5):999-1008. doi: 10.1016/j.bja.2017.12.046. Epub 2018 Mar 9.
Results Reference
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PubMed Identifier
30794305
Citation
Ravi B, Pincus D, Choi S, Jenkinson R, Wasserstein DN, Redelmeier DA. Association of Duration of Surgery With Postoperative Delirium Among Patients Receiving Hip Fracture Repair. JAMA Netw Open. 2019 Feb 1;2(2):e190111. doi: 10.1001/jamanetworkopen.2019.0111.
Results Reference
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Dexmedetomidine Supplemented Analgesia and Delirium After Hip Fracture Surgery

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