Anæstesi og perioperative neurokognitive lidelser hos ældre patienter, der gennemgår hoftefrakturkirurgi Platformforsøg (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 Enhanced Anesthesia Technique in Perioperative Neurocognitive Function, as Compared to Standard Anesthesia Care in the Elderly Patients Undergoing Hip Fracture
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.
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
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.
The study also includes a non-surgical cognitive control cohort. Members of this cohort do not undergo study randomization and do not receive any trial intervention. The cohort is used to help characterize changes associated with repeated cognitive testing and changes in cognition over time in the absence of surgery.
The platform allows interventions to be introduced, modified, advanced, or discontinued in accordance with the master protocol and applicable intervention-specific subprotocols. Accumulating safety and effectiveness data are reviewed by the independent Data Monitoring Committee. The committee makes recommendations to the Trial Steering Committee, which is responsible for platform decisions in accordance with the prespecified adaptive decision framework.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiekontakt
- Navn: Ting Li, MD, PhD
- Telefonnummer: 13587876896
- E-mail: liting1021@aliyun.com
Studiesteder
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Zhejiang
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Dongyang, Zhejiang, Kina
- Tilmelding efter invitation
- Dongyang People's Hospital
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Hangzhou, Zhejiang, Kina
- Tilmelding efter invitation
- Zhejiang Provincial People's Hospital
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Jinhua, Zhejiang, Kina
- Rekruttering
- Jinhua Municipal Central Hospital
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Kontakt:
- Yuanliang Chen, MD
- E-mail: chenyl1186@163.com
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Lishui, Zhejiang, Kina
- Rekruttering
- Lishui People's Hospital
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Kontakt:
- Jimin Wu, MD
- E-mail: wujimin2022@163.com
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Lishui, Zhejiang, Kina
- Rekruttering
- Lishui Central Hospital, the Fifth Hospital Affiliated to Wenzhou Medical University
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Kontakt:
- Chuanguang Wang, MD
- E-mail: wcg0033@wmu.edu.cn
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Ningbo, Zhejiang, Kina
- Rekruttering
- Ningbo No.2 Hospital
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Kontakt:
- Junping Chen, MD
- E-mail: 13858222873@163.com
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Ningbo, Zhejiang, Kina
- Rekruttering
- Ningbo No.6 Hospital
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Kontakt:
- Liyong Yuan, MD
- E-mail: ylysgl@hotmail.com
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Quzhou, Zhejiang, Kina
- Rekruttering
- Quzhou People's Hospital
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Kontakt:
- Xiangyu Fang, MD
- E-mail: 15811076@qq.com
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Taizhou, Zhejiang, Kina
- Tilmelding efter invitation
- Taizhou Central Hospital
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Taizhou, Zhejiang, Kina
- Tilmelding efter invitation
- Zhejiang Taizhou Hospital
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Wenling, Zhejiang, Kina
- Rekruttering
- The First People's Hospital of Wenling
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Kontakt:
- Yanguo Zheng, MD
- E-mail: zygm15@126.com
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Wenzhou, Zhejiang, Kina, 325000
- Rekruttering
- The Second Affilliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
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Kontakt:
- Ting Li, PhD
- Telefonnummer: 13587876896
- E-mail: liting1021@aliyun.com
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Ledende efterforsker:
- Ting Li, PhD
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Underforsker:
- Bingwu Huang, PhD
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Wenzhou, Zhejiang, Kina, 325000
- Tilmelding efter invitation
- The First Affiliated Hospital of Wenzhou Medical University
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Forebyggelse
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Enkelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: 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. |
Participants 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 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. For 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. For 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. Among 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. Among 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. |
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Eksperimentel: 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. |
Standard 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. Among 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. Among 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. Participants 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. |
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Aktiv komparator: 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. |
Standard 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. Among 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. Among 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. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Incidence of Neurocognitive Disorders (NCD) events rate during the first 7 postoperative days
Tidsramme: during the first 7 postoperative days
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Neurocognitive Disorders includes:
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. |
during the first 7 postoperative days
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Indlæggelsens længde
Tidsramme: dage fra indlæggelse til udskrivelse, i gennemsnit 7 dage
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dage fra indlæggelse til udskrivelse, i gennemsnit 7 dage
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Dage hjemme op til 30 dage efter operationen (DAH30)
Tidsramme: op til 30 dage efter operationen
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op til 30 dage efter operationen
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1-års dødelighed af alle årsager
Tidsramme: 1 år efter operationen
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1 år efter operationen
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Subtypes, severity, and duration of delirium
Tidsramme: during the first 7 postoperative days
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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
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Neurocognitive decline in postoperative 7 days
Tidsramme: during the first 7 postoperative days
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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. |
during the first 7 postoperative days
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Delayed neurocognitive recovery during 30 postoperative days
Tidsramme: Postoperative day 11 ± 3 days if the hospital stay exceeds 7 days, and postoperative day 30 ± 7 days.
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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. |
Postoperative day 11 ± 3 days if the hospital stay exceeds 7 days, and postoperative day 30 ± 7 days.
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Hospital Anxiety and Depression Scale (HADs)
Tidsramme: 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.
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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.
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Acute pain before and after surgery
Tidsramme: Before surgery and on postoperative days 1, 2, and 3.
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Using Visual Analogue Scale (VAS) |
Before surgery and on postoperative days 1, 2, and 3.
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Incidence of important intraoperative adverse events requiring treatment
Tidsramme: During anesthesia on the day of surgery.
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Important intraoperative adverse events are defined as adverse events requiring treatment. |
During anesthesia on the day of surgery.
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Complications (except cognitive impairment)
Tidsramme: during postoperation 30 days
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including pulmonary infection, myocardial infarction, renal failure, gastrointestinal obstruction, etc. |
during postoperation 30 days
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In-hospital and 30-day mortality
Tidsramme: During hospitalization and within 30 days after surgery.
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During hospitalization and within 30 days after surgery.
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Score of EuroQol Five Dimensions Questionnaire (EQ-5D)
Tidsramme: 1 week before fracture (retrospective assessment), and 1, 3, 6, 9, and 12 months after surgery.
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Quality of life will be assessed using the EuroQol Five Dimensions Questionnaire (EQ-5D). Prefracture quality of life will be assessed retrospectively for the week before fracture. |
1 week before fracture (retrospective assessment), and 1, 3, 6, 9, and 12 months after surgery.
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Incidence of postoperative Neurocognitive Disorders (NCD)
Tidsramme: Up to 12 months after surgery.
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Postoperative neurocognitive disorder will be determined as a binary outcome according to the prespecified neurocognitive assessment framework. Cognitive assessments, including the Mini-Mental State Examination, Montreal Cognitive Assessment, multidomain neuropsychological tests, and patient- or caregiver-reported cognitive change, will be integrated according to the prespecified criteria to determine whether postoperative neurocognitive disorder is present. The reported outcome is the proportion of participants with postoperative neurocognitive disorder. |
Up to 12 months after surgery.
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Severity of postoperative Neurocognitive Disorders (NCD)
Tidsramme: At 12 months after surgery
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At 12 months after surgery
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Type of postoperative Neurocognitive Disorders (NCD)
Tidsramme: within 1 year after surgery (long-term)
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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)
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Instrumental Activities of Daily Living (IADL)
Tidsramme: 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.
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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.
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Health economic outcomes
Tidsramme: 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.
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Health economic outcomes include direct medical costs, direct nonmedical costs, and indirect costs. Direct medical costs include anesthesia and related costs, surgical treatment costs, medication and biological product costs, diagnosis-related costs, supportive treatment costs, rehabilitation costs, blood and blood product costs, and consumable material costs. Direct nonmedical costs include paid caregiver costs, transportation costs, and accommodation costs related to medical care. Indirect costs mainly include productivity losses of family members or unpaid caregivers due to accompanying or caring for the participant. |
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.
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Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Incidence of adverse events
Tidsramme: From enrollment to hospital discharge, an average of 7 days.
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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:
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From enrollment to hospital discharge, an average of 7 days.
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Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Ting Li, MD, PhD, Second Affiliated Hospital of Wenzhou Medical University
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Hjernesygdomme
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- Psykiske lidelser
- Sår og skader
- Benskader
- Neurokognitive lidelser
- Kognitionsforstyrrelser
- Brud, Knogle
- Lårbensbrud
- Hofteskader
- Kognitiv dysfunktion
- Hoftebrud
- Demens
- Kirurgiske procedurer, operative
- Anæstesi og analgesi
- Neurokirurgiske procedurer
- Anæstesi, ledning
- Anæstesi
- Denervering
- Nerveblok
Andre undersøgelses-id-numre
- SAHoWMU-CR2024-03-112
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Within 1 year after study completion, study data and related documentation will be made available upon request to the principal investigator or data coordinating center. The documentation will include annotated case report forms, descriptions of the structure, variables, and content of each dataset, the final protocol, study procedures, data collection forms, descriptions of variable recoding, and lists and links to major publications. Key datasets will be archived as appropriate.
IPD-delingstidsramme
Available within 1 year after study completion.
IPD-delingsadgangskriterier
Requests should be submitted to the principal investigator or data coordinating center.
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
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