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Dexmedetomidine Supplemented Intravenous Analgesia in Elderly After Orthopedic Surgery

Primary Purpose

Elderly, Orthopedic Surgery, Analgesia

Status

Unknown status

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Dexmedetomidine

Placebo

About this trial

This is an interventional prevention trial for Elderly focused on measuring Elderly, Orthopedic Surgery, Analgesia, Dexmedetomidine, Postoperative Delirium, Long-term Outcome

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 total knee/hip replacement surgery, or spinal 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 Hospital
Beijing Jishuitan Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dexmedetomidine group

Control group

Arm Description

For patients in the dexmedetomidine group, postoperative analgesia is provided in the form of patient-controlled intravenous analgesia. The formula contains a mixture of sufentanil (1.25 ug/ml) and dexmedetomidine (1.25 ug/ml), diluted with normal saline to a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a patient-controlled bolus of 2 ml each time and a lockout interval of 8 minutes.

For patients in the control group, postoperative analgesia is provided in the form of patient-controlled intravenous analgesia. The formula contains a mixture of placebo and sufentanil (1.25 ug/ml), diluted with normal saline to a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a patient-controlled bolus of 2 ml each time and a lockout interval of 8 minutes.

Outcomes

Primary Outcome Measures

Incidence of delirium within the first 5 days after surgery

Secondary Outcome Measures

Daily prevalence of delirium during the first 5 days after surgery

Length of stay in hospital after surgery

Incidence of non-delirium complications with 30 days after surgery

All-cause 30-day mortality

Quality of life of 30-day survivors

Quality of life of 30-day survivors is assessed with World Health Organization Quality of Life brief version (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 of 30-day survivors

Cognitive function of 30-day survivors is assessed with the modified Telephone Interview for Cognitive Status (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 48, with higher score indicating better function.

Agitation or sedation level during postoperative days 1-5

Agitation or 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).

Cumulative sufentanil consumption within 5 postoperative days

Pain severity during postoperative days 1-5

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.

Subjective sleep quality during postoperative days 1-5

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.

Overall survival for up to 3 years after surgery

Time from surgery to all-cause death for up to 3 years after surgery.

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 procedure.

Quality of life in 1-，2- and 3-year survivors after surgery

Quality of life in 1-，2- and 3-year survivors 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 in 1-，2- and 3-year survivors 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 48, with higher score indicating better function.

Full Information

NCT ID

NCT03629262

First Posted

August 8, 2018

Last Updated

July 5, 2021

Sponsor

Peking University First Hospital

Collaborators

Beijing Jishuitan Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03629262

Brief Title

Dexmedetomidine Supplemented Intravenous Analgesia in Elderly After Orthopedic Surgery

Official Title

Impact of Dexmedetomidine Supplemented Intravenous Analgesia on Postoperative Delirium and Long-term Outcomes in Elderly After Orthopedic Surgery: A Multicenter, Double-blinded, Randomized Controlled Trial

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Unknown status

Study Start Date

October 28, 2018 (Actual)

Primary Completion Date

December 6, 2019 (Actual)

Study Completion Date

December 7, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University First Hospital

Collaborators

Beijing Jishuitan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Delirium is common in the elderly after orthopedic surgery and is associated with worse outcomes. The investigators hypothesize that, for elderly patients after orthopedic surgery, dexmedetomidine supplemented intravenous analgesia can reduce the incidence of delirium and improve the long-term outcomes.

Detailed Description

A growing number of elderly patients undergo orthopedic surgery each year. Delirium is a common complication in these patients after 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. 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 intravenous analgesia (in the form of patient-controlled analgesia) can also reduce delirium and improve long-term outcomes in elderly patients after orthopedic surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Elderly, Orthopedic Surgery, Analgesia, Dexmedetomidine, Postoperative Delirium, Long-term Outcome

Keywords

Elderly, Orthopedic Surgery, Analgesia, Dexmedetomidine, Postoperative Delirium, Long-term Outcome

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

712 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dexmedetomidine group

Arm Type

Experimental

Arm Description

Arm Title

Control group

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Dexmedetomidine

Other Intervention Name(s)

Sufentanil analgesia

Intervention Description

Patients in this group receive patient-controlled intravenous analgesia for 1-3 days after surgery. The formula is a mixture of dexmedetomidine (1.25 ug/ml) and sufentanil (1.25 ug/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Sufentanil analgesia

Intervention Description

Patients in this group receive patient-controlled intravenous analgesia for 1-3 days after surgery. The formula is a mixture of placebo and sufentanil (1.25 ug/m), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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

Incidence of delirium within the first 5 days after surgery

Time Frame

The first 5 days after surgery

Secondary Outcome Measure Information:

Title

Daily prevalence of delirium during the first 5 days after surgery

Description

Daily prevalence of delirium during the first 5 days after surgery

Time Frame

The first 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 with 30 days after surgery

Description

Incidence of non-delirium complications with 30 days after surgery

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 of 30-day survivors

Description

Time Frame

At 30 days after surgery

Title

Cognitive function of 30-day survivors

Description

Time Frame

At 30 days after surgery

Title

Agitation or sedation level during postoperative days 1-5

Description

Time Frame

The first 1-5 days after surgery

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

The first 1-5 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

The first 1-5 days after surgery

Title

Overall survival for up to 3 years after surgery

Description

Time from surgery to all-cause death for up to 3 years after surgery.

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 procedure.

Time Frame

Up to 3 years after surgery

Title

Quality of life in 1-，2- and 3-year survivors after surgery

Description

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

Time Frame

At the end of the 1st, 2nd, and 3rd year after surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Maximum Age & Unit of Time

89 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 65 years but < 90 years; Scheduled to undergo total knee/hip replacement surgery, or spinal 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dong-Xin Wang, MD, PhD

Organizational Affiliation

Peking University First Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Peking University First Hospital

City

Beijing

ZIP/Postal Code

100034

Country

China

Facility Name

Beijing Jishuitan Hospital

City

Beijing

Country

China

12. IPD Sharing Statement

Plan to Share IPD

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Dexmedetomidine Supplemented Intravenous Analgesia in Elderly After Orthopedic Surgery

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