The ANDES Platform Trial is a pragmatic, multicenter, adaptive randomized controlled platform trial in patients aged 65 years or older undergoing surgery for hip fracture. The trial evaluates whether enhanced anesthesia techniques reduce perioperative neurocognitive disorders compared with standard anesthesia care.
The platform includes two randomization processes. In the first randomization, eligible participants are assigned to an active platform intervention-currently a preoperative regional nerve block or perioperative intravenous lidocaine infusion-or to a shared standard-anesthesia control. Participants for whom general anesthesia is planned may also enter a second, nested randomization and are assigned in a fixed 1:1 ratio to total intravenous anesthesia or volatile inhalational anesthesia, regardless of whether they participate in the first randomization.
A non-surgical cognitive control cohort is included to characterize changes in cognitive test performance over time without exposure to surgery or study interventions. The Data Monitoring Committee reviews accumulating trial data and makes recommendations to the Trial Steering Committee, which determines whether platform interventions should continue, be modified, advance, or stop.
Aged 65 years and older.
Patients with unilateral hip fracture (including femoral neck, femoral head, intertrochanteric and subtrochanteric fractures) are scheduled for surgical treatment.
American Society of Anesthesiologists (ASA) physical status IV or below.
The patients or family members provide written informed consent.
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.);
Two or more anesthetic surgeries are required.
Patients with an obvious history of head trauma (such as loss of consciousness for more than 5 minutes, post-traumatic amnesia, etc.);
Patients who the researcher believes are unable to complete the assessment of primary outcome;
Parallel
Nerve block
Procedure/SurgeryParticipants receive a preoperative regional nerve block as soon as possible after randomization. Ultrasound guidance is recommended, and fascia iliaca block is the recommended block technique.
Standard anesthesia care
Procedure/SurgeryStandard anesthesia care consists of routine general or regional anesthesia according to usual practice at each study center. Participants randomized to the shared control group do not receive protocol-specified trial interventions unless otherwise required by the Trial Steering Committee. Changes to standard anesthesia care are made in accordance with the prespecified adaptive decision framework. The independent Data Monitoring Committee reviews accumulating data and makes recommendations to the Trial Steering Committee, which makes the final platform decisions.
Bupivacaine liposome
DrugFor participants randomized to the nerve block group, 1.33% bupivacaine liposome is recommended as a long-acting local anesthetic, with a maximum dose not exceeding 133 mg, to maintain the continuity of the nerve block effect.
Regular local anesthetic
DrugFor participants randomized to the nerve block group, regular local anesthetic, such as bupivacaine or ropivacaine, may be used with continuous electronic analgesic pump infusion or multiple single injections to maintain the continuity of the nerve block effect.
Intravenous infusion of lidocaine
DrugParticipants randomized to the lidocaine group receive ECG monitoring, oxygen saturation monitoring, blood pressure monitoring, and an open intravenous route on the morning of surgery. It is recommended to start the infusion of lidocaine as soon as possible in the ward. A portable electronic infusion pump is recommended for drug delivery. The loading dose is 1 mg/kg, and the maintenance dose range is 1 to 2 mg/kg/h. The specific dose is determined by the anesthesiologist according to 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 are recorded. Intravenous infusion of lidocaine should be administered under ECG monitoring.
Total intravenous anesthesia maintenance
Procedure/SurgeryAmong participants who are eligible under the master protocol and for whom general anesthesia is planned, anesthetic maintenance may be assigned by the second nested randomization to total intravenous anesthesia maintenance in a 1:1 ratio. Total intravenous anesthesia maintenance is recommended to be mainly propofol-based, and analgesics such as remifentanil or fentanyl are recommended.
Volatile anesthesia maintenance
Procedure/SurgeryAmong participants who are eligible under the master protocol and for whom general anesthesia is planned, anesthetic maintenance may be assigned by the second nested randomization to volatile anesthesia maintenance in a 1:1 ratio. Following intravenous induction, anesthesia maintenance mainly with sevoflurane or isoflurane is recommended.
Incidence of Neurocognitive Disorders (NCD) events rate during the first 7 postoperative days
Neurocognitive Disorders includes: 1. Postoperative delirium (POD) was mesaured by 3D-CAM; 2. 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 domains (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). Neurocognitive function is assessed at screening, postoperative day 3, and postoperative day 7. If discharge occurs on postoperative day 5 or 6, the final assessment is performed on the day of discharge; if discharge occurs on postoperative day 4, no repeat cognitive assessment is performed. A participant with postoperative delirium and/or postoperative neurocognitive decline is classified as positive for the primary outcome.
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.
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 domains (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.
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 domains(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.
Hospital Anxiety and Depression Scale (HADs)
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: 1. cardiopulmonary resuscitation; 2. Malignant hyperthermia or anaphylaxis; 3. Aspiration pneumonia ; 4. Epidural hematoma requiring surgical intervention within 24 hours after regional anesthesia; 5. Lower-limb paralysis lasting more than 24 hours after regional anesthesia or nerve block; 6. Unplanned postoperative mechanical ventilation lasting more than 6 hours in patients who did not require mechanical ventilation before surgery; 7. Other adverse events during postoperative hospitalization.
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Second Affiliated Hospital of Wenzhou Medical University
Lead sponsor
Zhejiang Provincial People's Hospital
Collaborator
First Affiliated Hospital of Wenzhou Medical University
Collaborator
Ningbo No.2 Hospital
Collaborator
Ningbo No.6 Hospital
Collaborator
Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
Collaborator
Taizhou Hospital
Collaborator
Affiliated Wenling Hospital of Wenzhou Medical University
Collaborator
Lishui Country People's Hospital
Collaborator
The Fifth Hospital Affiliated to Wenzhou Medical University/ Lishui Central Hospital
Collaborator
Jinhua Municipal Central Hospital
Collaborator
Dongyang People's Hospital
Collaborator
People's Hospital of Quzhou
Collaborator
