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 Enhanced Anesthesia Technique in Perioperative Neurocognitive Function, as Compared to Standard Anesthesia Care in the Elderly Patients Undergoing Hip Fracture
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,860
- 试验地点
- 14
- 主要终点
- Incidence of Neurocognitive Disorders (NCD) events rate during the first 7 postoperative days
研究概览
简要总结
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.
详细描述
The ANDES Platform Trial is a pragmatic, multicenter, adaptive platform trial designed to evaluate anesthesia strategies for reducing perioperative neurocognitive disorders in older patients undergoing hip fracture surgery.
The trial includes two related randomization processes.
In the first randomization, participants who meet the eligibility criteria for a specific platform intervention are randomly assigned to that intervention or to shared standard anesthesia care. The current platform interventions include preoperative regional nerve block and perioperative intravenous lidocaine infusion. Each intervention is compared with control participants who were eligible for randomization to that intervention.
Participants for whom the responsible anesthesiologist plans to use general anesthesia may enter a second, nested randomization, irrespective of their participation in the first randomization. These participants are assigned in a fixed 1:1 ratio to one of two anesthetic-maintenance strategies: total intravenous anesthesia, for which propofol-based maintenance is recommended, or volatile anesthesia, for which maintenance mainly with sevoflurane or isoflurane is recommended following intravenous induction.
Patients and treating clinicians are not blinded because of the nature of the interventions. Where implemented as specified in the protocol, outcome assessors remain unaware of treatment allocation, and statistical analyses are conducted using blinded treatment codes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
Participants and treating clinicians are not blinded because of the nature of the interventions. Outcome assessors are blinded to treatment allocation. Statistical analyses are conducted using blinded treatment codes.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
- •Additional inclusion criteria may pertain to specific interventions and will be described in relevant sub-protocols.
排除标准
- •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;
- •Additional exclusion criteria may pertain to specific interventions and will be described in relevant sub-protocols.
- •Additional exclusion criteria for the nerve block randomization:
- •Contraindications to nerve block, including allergy to local anesthetics, other contraindications specified in the applicable prescribing information, infection at the puncture site, or refusal to receive nerve block;
- •The investigator considers the participant unsuitable for nerve block because of conditions such as a history of severe peripheral neuropathy or severe coagulation dysfunction;
- •Receipt of nerve block before randomization during the current hospitalization.
- •Additional exclusion criteria for the intravenous lidocaine randomization:
- •Allergy to lidocaine;
- •Severe hepatic impairment or renal insufficiency for which the investigator considers the participant unsuitable for enrollment.
- •Eligibility Criteria for nonsurgical cognitive control participants:
- •A nonsurgical cognitive control cohort may be recruited from emergency departments, outpatient clinics, inpatient wards, or the community for standardization of neurocognitive assessments. These participants will be matched as far as possible to surgical participants by age and education level. Except for criteria related to hip fracture surgery and trial interventions, the same general inclusion and exclusion criteria will apply. Nonsurgical cognitive control participants must not undergo surgery or anesthesia during the observation period; participants who undergo surgery during follow-up will be excluded from the nonsurgical cognitive control cohort.
研究组 & 干预措施
Nerve block
Participants receive standard anesthesia care plus preoperative regional nerve block, as described in sub-trial protocol 1. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Nerve block (Procedure)
Nerve block
Participants receive standard anesthesia care plus preoperative regional nerve block, as described in sub-trial protocol 1. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Standard anesthesia care (Procedure)
Nerve block
Participants receive standard anesthesia care plus preoperative regional nerve block, as described in sub-trial protocol 1. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Regular local anesthetic (Drug)
Nerve block
Participants receive standard anesthesia care plus preoperative regional nerve block, as described in sub-trial protocol 1. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Total intravenous anesthesia maintenance (Procedure)
Nerve block
Participants receive standard anesthesia care plus preoperative regional nerve block, as described in sub-trial protocol 1. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Volatile anesthesia maintenance (Procedure)
Intravenous infusion of lidocaine
Participants receive standard anesthesia care plus perioperative intravenous lidocaine infusion, as described in sub-trial protocol 2. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Standard anesthesia care (Procedure)
Intravenous infusion of lidocaine
Participants receive standard anesthesia care plus perioperative intravenous lidocaine infusion, as described in sub-trial protocol 2. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Intravenous infusion of lidocaine (Drug)
Intravenous infusion of lidocaine
Participants receive standard anesthesia care plus perioperative intravenous lidocaine infusion, as described in sub-trial protocol 2. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Total intravenous anesthesia maintenance (Procedure)
Intravenous infusion of lidocaine
Participants receive standard anesthesia care plus perioperative intravenous lidocaine infusion, as described in sub-trial protocol 2. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Volatile anesthesia maintenance (Procedure)
Shared standard anesthesia care
Participants receive standard anesthesia care. Participants for whom general anesthesia is planned may also enter the second nested randomization and be assigned in a fixed 1:1 ratio to total intravenous anesthesia maintenance or volatile anesthesia maintenance.
干预措施: Standard anesthesia care (Procedure)
Shared standard anesthesia care
Participants receive standard anesthesia care. Participants for whom general anesthesia is planned may also enter the second nested randomization and be assigned in a fixed 1:1 ratio to total intravenous anesthesia maintenance or volatile anesthesia maintenance.
干预措施: Total intravenous anesthesia maintenance (Procedure)
Shared standard anesthesia care
Participants receive standard anesthesia care. Participants for whom general anesthesia is planned may also enter the second nested randomization and be assigned in a fixed 1:1 ratio to total intravenous anesthesia maintenance or volatile anesthesia maintenance.
干预措施: Volatile anesthesia maintenance (Procedure)
Nerve block
Participants receive standard anesthesia care plus preoperative regional nerve block, as described in sub-trial protocol 1. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.
干预措施: Bupivacaine liposome (Drug)
结局指标
主要结局
Incidence of Neurocognitive Disorders (NCD) events rate during the first 7 postoperative days
时间窗: 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.
次要结局
- Instrumental Activities of Daily Living (IADL)(At screening for the week before fracture, postoperative day 5 ± 2 days, postoperative day 11 ± 3 days if the hospital stay exceeds 7 days, postoperative day 30 ± 7 days, and postoperative months 3, 6, 9, and 12.)
- Delayed neurocognitive recovery during 30 postoperative days(Postoperative day 11 ± 3 days if the hospital stay exceeds 7 days, and postoperative day 30 ± 7 days.)
- Hospital Anxiety and Depression Scale (HADs)(At screening, postoperative day 5 ± 2 days, postoperative day 11 ± 3 days if the hospital stay exceeds 7 days, postoperative day 30 ± 7 days, and postoperative month 12 ± 1 month.)
- Acute pain before and after surgery(Before surgery and on postoperative days 1, 2, and 3.)
- Incidence of important intraoperative adverse events requiring treatment(During anesthesia on the day of surgery.)
- In-hospital and 30-day mortality(During hospitalization and within 30 days after surgery.)
- Score of EuroQol Five Dimensions Questionnaire (EQ-5D)(1 week before fracture (retrospective assessment), and 1, 3, 6, 9, and 12 months after surgery.)
- Incidence of postoperative Neurocognitive Disorders (NCD)(Up to 12 months after surgery.)
- Severity of postoperative Neurocognitive Disorders (NCD)(At 12 months after surgery)
- Health economic outcomes(During hospitalization; from hospital discharge to the 1-month follow-up; and for each interval from the previous follow-up visit to the 3-, 6-, 9-, and 12-month follow-up visits.)
- Score of EuroQol Five Dimensions Questionnaire (EQ-5D)(1 week before fracture (review); 1 month; 6 months; and 12 months after surgery.)
- Instrumental Daily Living Ability Scale (IADL)(within 1 year after surgery (long-term))
- Economic indicators(during the entire trial, an average of 1 year.)
- Neurocognitive decline in postoperative 7 days(during the first 7 postoperative days)
- Incidence of postoperative Neurocognitive Disorders (NCD)(within 1 year after surgery (long-term))
- Mortality(30 days)
- Type of postoperative Neurocognitive Disorders (NCD)(within 1 year after surgery (long-term))
- Delayed neurocognitive recovery during 30 postoperative days(during 30 postoperative days)
- Hospital Anxiety and Depression Scale (HADs)(during postoperative one year)
- Length of hospitalization(days from admission to discharge, an average of 7 days)
- Complications (except cognitive impairment)(during postoperation 30 days)
- Days at home up to 30 days after surgery (DAH30)(up to 30 days after surgery)
- Severity of postoperative Neurocognitive Disorders (NCD)(within 1 year after surgery (long-term))
- Subtypes, severity, and duration of delirium(during the first 7 postoperative days)
- Acute pain before surgery(1, 2, 3 days after surgery)
- 1-year all-cause mortality(1-year after surgery)