Anesthesia and Perioperative Neurocognitive Disorders in the Elderly Patients Undergoing Hip Fracture Surgery Platform Trial (ANDES Platform Trial) (ANDES platform)

Anesthesia and Perioperative Neurocognitive Disorders in the Elderly Patients Undergoing Hip Fracture Surgery Platform Trial (ANDES Platform Trial): A Pragmatic Multi-arm, Adaptive, Open Label, Multicenter Randomized Controlled Platform Trial to Assess the Effect of Different Enhance Anesthesia Technique in Perioperative Neurocognitive Function, as Compared to Standard Anesthesia Care in the Elderly Patients Undergoing Hip Fracture

Anesthesia and perioperative Neurocognitive Disorders in the Elderly patients undergoing hip fracture Surgery platform trial (ANDES platform trial): A pragmatic multi-arm, adaptive, open label, multicenter randomized controlled platform trial to assess the effect of different enhance anesthesia technique in perioperative neurocognitive function, as compared to standard anesthesia care in the elderly patients undergoing hip fracture

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Dementia; Hip Fractures; Anesthesia; Cognitive Decline
• Intervention / Treatment: Other: Nerve block+standard anesthesia; Drug: Bupivacaine liposome; Device: Ultrasound-guided nerve block; Drug: Intravenous lidocaine+standard anesthesia

• Study Type: Interventional
• Enrollment (Estimated): 1860
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The Second Affilliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
      • Contact: Ting Li, PhD; Phone Number: 13587876896; Email: liting1021@aliyun.com
      • Principal Investigator: Ting Li, PhD
      • Sub-Investigator: Bingwu Huang, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Aged 65 years and older.
2. Patients with unilateral hip fracture (including femoral neck, femoral head, intertrochanteric and subtrochanteric fractures) are scheduled for surgical treatment.
3. American Society of Anesthesiologists (ASA) physical status IV or below.
4. The patients or family members provide written informed consent.
5. Additional inclusion criteria may pertain to specific interventions and will be described in relevant sub-protocols.

Exclusion Criteria:

1. Patients with multiple trauma or fractures (excluding trauma that the researcher judges will not affect the patient's overall recovery, such as simple spinal compression fractures, mild soft tissue contusions, fractures of hands and feet, etc.);
2. Two or more anesthetic surgeries are required.
3. Petients with an obvious history of head trauma (such as loss of consciousness for more than 5 minutes, post-traumatic amnesia, etc.);
4. Patients who the researcher believes are unable to complete the assessment of primary outcome;
5. Additional exclusion criteria may pertain to specific interventions and will be described in relevant sub-protocols.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nerve block + standard anesthesia protocol; (described in detail in sub-trial protocol 1)	Other: Nerve block+standard anesthesia; Receive nerve block as soon as possible after randomization;; Ultrasound-guided nerve block is recommended, with the iliacfascia block recommended as the blocking site;; It is recommended to use 1.33% bupivacaine liposome (long-acting), and the maximum dose should not exceed 133mg; or regular local anesthetic (bupivacaine or ropivacaine, etc.) with electronic analgesic pumping infusion; or multiple single injections of regular local anesthetics should be used to maintain the continuity of nerve block effect.; Drug: Bupivacaine liposome; 1.33% bupivacaine liposome; Device: Ultrasound-guided nerve block; Ultrasound-guided nerve block
Experimental: Intravenous infusion of lidocaine + standard anesthesia protocol; (described in detail in sub-trial protocol 2)	Drug: Intravenous lidocaine+standard anesthesia; Subjects randomly assigned to Lidocaine Group (Group L) will be given ECG monitoring, oxygen saturation monitoring, blood pressure monitoring and an open intravenous route on the morning of the surgery. It is recommended to start the infusion of Lidocaine as soon as possible in the ward.; It is recommended to use portable electronic infusion pump for drug delivery. The loading dose is 1mg/kg, and the maintenance dose range is 1~2mg/kg/h. The specific dosage is determined by the anesthesiologist based on the patient's condition. The infusion ends when the patient leaves the Post-anesthesia care unit after surgery, and the infusion time and total amount should be recorded.
No Intervention: Standard anesthesia protocol; (If an intervention was found to be effective in the interim analysis, the executive committee will decide whether to add it to the standard anesthesia protocol.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Neurocognitive Disorders (NCD) events rate during the first 7 postoperative days	Neurocognitive Disorders includes: Postoperative delirium (POD) was mesaured by 3D-CAM;; Neurocognitive decline was mesaured within 7 postoperative days by: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), and neuropsychological tests containing 5 cognitive latitudes (1. digit span test (DST); 2. trail making test (TMT); 3. Boston naming test (BNT); 4. auditory verbal learning test-Huashan version (AVLT-H)；5. clock drawing test (CDT).）, and active report of patients or family members).	during the first 7 postoperative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		30 days
Subtypes, severity, and duration of delirium	Using CAM-S, and in units of days from the onset of delirium symptoms to the disappearance of symptoms or when the patient is discharged.	during the first 7 postoperative days
Neurocognitive decline in postoperative 7 days	Neurocognitive decline was mesaured by: Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA), or neuropsychological tests containing 5 cognitive latitudes (1. digit span test (DST); 2. trail making test (TMT); 3. Boston naming test (BNT); 4. auditory verbal learning test-Huashan version (AVLT-H)；5. clock drawing test (CDT).）, or active report of patients or family members.	during the first 7 postoperative days
Delayed neurocognitive recovery during 30 postoperative days	This was mesaured by: Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA), or neuropsychological tests containing 5 cognitive latitudes (1. digit span test (DST); 2. trail making test (TMT); 3. Boston naming test (BNT); 4. auditory verbal learning test-Huashan version (AVLT-H)；5. clock drawing test (CDT).）, or active report of patients or family members.	during 30 postoperative days
Hospital Anxiety and Depression Scale (HADs)		during postoperative one year
Acute pain before surgery	Using Visual Analogue Scale (VAS)	1, 2, 3 days after surgery
Length of hospitalization		days from admission to discharge, an average of 7 days
Complications (except cognitive impairment)	including pulmonary infection, myocardial infarction, renal failure, gastrointestinal obstruction, etc.	during postoperation 30 days
Days at home up to 30 days after surgery (DAH30)		up to 30 days after surgery
Score of EuroQol Five Dimensions Questionnaire (EQ-5D)	using EQ-5D to measure quality of life	1 week before fracture (review); 1 month; 6 months; and 12 months after surgery.
Incidence of postoperative Neurocognitive Disorders (NCD)	This was mesaured within 7 postoperative days by: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), and neuropsychological tests containing 5 cognitive latitudes (1. digit span test (DST); 2. trail making test (TMT); 3. Boston naming test (BNT); 4. auditory verbal learning test-Huashan version (AVLT-H)；5. clock drawing test (CDT).), and active report of patients or family members).	within 1 year after surgery (long-term)
Severity of postoperative Neurocognitive Disorders (NCD)	Includes major and mild postoperative NCD	within 1 year after surgery (long-term)
Type of postoperative Neurocognitive Disorders (NCD)	Using Hachinski Ischemic Scale (HIS) combined with clinical symptoms and auxiliary examination to mesaure the type of postoperative NCD. HIS ≥7 was considered as vascular cognitive impairment.	within 1 year after surgery (long-term)
Instrumental Daily Living Ability Scale (IADL)	IADL ≤6 is normal	within 1 year after surgery (long-term)
1-year all-cause mortality		1-year after surgery
Economic indicators	Hospitalization fees;; Preoperative fees;; Anesthesia fees;; Surgery fees;; Post-operative fees;; Post-discharge medical expenses.	during the entire trial, an average of 1 year.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	We will collect the following known potential risks of general and local anesthesia from the start of the intervention to the subject's discharge and assess the overall incidence: cardiopulmonary resuscitation;; Malignant hyperthermia or anaphylaxis;; Aspiration pneumonia ;; Epidural hematoma ; 6) Patients who did not need mechanical ventilation before surgery continued with unplanned mechanical ventilation for more than 6 hours after surgery; 7) Other adverse events during postoperative hospitalization.	during hospitalization, an average of 7 days; through entire trial, an average of 1 year.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Wenzhou Medical University
• Collaborators: Jinhua Municipal Central Hospital; Taizhou Hospital; Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University; Ningbo No.2 Hospital; People's Hospital of Quzhou; Lishui Country People's Hospital; The First People's Hospital of Wenling; Dongyang People's Hospital; Zhejiang Provincial People's Hospital/ People's Hospital of Hangzhou Medical College; The 1st Affiliated Hospital of Wenzhou Medical University; Ningbo No.6 Hospital; The Fifth Hospital Affiliated to Wenzhou Medical University/ Lishui Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2024
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: May 28, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 11, 2024

Study Record Updates

• Last Update Posted (Estimated): November 8, 2024
• Last Update Submitted That Met QC Criteria: November 7, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Wounds and Injuries; Leg Injuries; Cognition Disorders; Femoral Fractures; Hip Injuries; Cognitive Dysfunction; Fractures, Bone; Hip Fractures; Neurocognitive Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics, Local; Central Nervous System Depressants; Sensory System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Bupivacaine; Lidocaine; Anesthetics
• Other Study ID Numbers: SAHoWMU-CR2024-03-112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No