Perioperative Dexmedetomidine and Long-term Survival After Cancer Surgery

Elderly Clinical Trial

Official title:

Impact of Perioperative Dexmedetomidine on Long-term Survival in Older Patients After Cancer Surgery: a Multicenter Randomized Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06030804
• Other study ID #: 2023-227
• Status: Recruiting
• Phase: N/A
• Start date: September 12, 2023
• Est. completion date: October 2028

Study information

• Verified date: December 2023
• Source: Peking University First Hospital
• Contact: Dong-Xin Wang, MD,PhD
• Phone: 8610 83572784
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Along with aging population, cancer incidence and mortality are increasing. However, despite advances in oncology and surgery, long-term survival of cancer patients is far from optimal. Dexmedetomidine is a highly selective alpha 2 adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. Studies showed that perioperative use of dexmedetomidine reduces delirium and some non-delirium complications after surgery. In long-term follow-up studies of older patients who, for other reasons, were randomized to receive either dexmedetomidine or placebo during intra- or postoperative period, dexmedetomidine use was associated with improved long-term survival. This multicenter randomized trial aims to investigate the effect of perioperative dexmedetomidine on long-term outcomes in older patients undergoing cancer surgery.

Description:

Along with aging population, cancer incidence and mortality are increasing. Surgical resection remains the mainstay treatment for solid organ cancer. However, despite advances in oncology and surgery, long-term survival of cancer patients is far from optimal. For example, the 5-year survival rate of cancer patients is about 36.9% in China, and the survival rate decreases for about 10% each year in older patients after cancer surgery. How to improve long-term survival after cancer surgery remains an urgent problem to be solved.

Cancer death usually occur after cancer recurrence or metastasis. The development of cancer recurrence or metastasise after surgical resection depends on the balance between the anti-cancer defense function of host and the invasiveness of residual cancer cells. Studies showed that surgery, while resecting cancer mass, also releases cancer cells into the circulation. Surgical stress also impairs cell-mediated immunity and promote cancer growth.

Dexmedetomidine is a highly selective alpha 2 adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. Studies showed that intraoperative use of dexmedetomidine reduces anesthetic and opioid consumption and relieves surgery-related stress response and inflammation. Studies also showed that perioperative use of dexmedetomidine reduces delirium, a commonly occurred complication in older patients, and some non-delirium complications after surgery.

The effect of perioperative dexmedetomidine on long-term outcomes after cancer surgery remains unclear. In a long-term follow-up of older patients who were randomized to receive either low-dose dexmedetomidine or placebo during intensive care unit stay, dexmedetomidine use was associated with improved survival within 2 years. In a recent long-term follow-up of older patients who were randomized to receive either dexmedetomidine or placebo during surgery, dexmedetomidine use was associated with improved recurrence-free survival.

The investigators hypothesize that perioperative use of dexmedetomidine may improve long-term survival after cancer surgery. This multicenter randomized trial aims to investigate the effect of perioperative dexmedetomidine on long-term outcomes in older patients undergoing cancer surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4532
• Est. completion date: October 2028
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion criteria:

1. Aged 60 years or older.

2. Scheduled to undergo radical surgery for cancer under general anesthesia, with an expected surgical duration of 2 hours or longer.

3. Required patient-controlled intravenous analgesia after surgery.

Exclusion criteria:

1. Inability to communicate preoperatively due to visual, auditory, verbal. or other reasons.

2. Surgery for breast cancer or intracranial tumor.

3. Preoperative severe sinus bradycardia (<50 beats per minute), sick sinus syndrome,or second-degree or above atrioventricular block without pacemaker.

4. Severe hepatic dysfunction (Child-Pugh class C).

5. Severe renal dysfunction (requirement of renal replacement therapy before surgery).

6. Enrolled in other clinical studies.

Related Conditions & MeSH terms

• Dexmedetomidine
• Elderly
• Long-Term Survivors

Intervention

Drug:
• Dexmedetomidine
A loading dose of dexmedetomidine (0.6 µg/kg) will be administered over 10-15 minutes before anaesthesia induction, followed by a continuous infusion at a rate of 0.5 µg/kg/hr till 1 hour before the end of surgery. Patient-controlled dexmedetomidine supplemented sufentanil analgesia will be provided after surgery: the formula contains a mixture of sufentanil (1.25 µg/ml) and dexmedetomidine (1.25 µg/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 patient-controlled bolus of 2 ml each time and a lockout time of 8 minutes.
• Placebo
Volume-matched normal saline will be administered in the same rate and volume for the same duration as in the dexmedetomidine group during anesthesia. Patient-controlled sufentanil analgesia will be provided after surgery: the formula contains sufentanil (1.25 µg/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 patient-controlled bolus of 2 ml each time and a lockout time of 8 minutes.

Locations

Country	Name	City	State
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing, China
China	Tsinghua University Yuquan Hospital	Beijing	Beijing
China	Bethune First Hospital Of Jilin University	Changchun	Jilin
China	Xiangya Hospital Central south university	Changsha	Hunan
China	The First Affiliated Hospital of Army Medical University (Southwest Hospital)	Chongqing	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Fujian Provincial Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	The Second Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The First Affiliated Hospital of China University of Science and Technology	Hefei	Hebei
China	The First Affiliated Hospital of China University of Science and Technology(Anhui Provincial Hospital)	Hefei	Hebei
China	The First Affiliated Hospital of University of South China	Hengyang	Hunan
China	Shandong Provincial Hospital Heze Hospital	Heze	Shandong
China	Affiliated Drum Tower Hospital, Medical School of Nanjing University	Nanjing	Jiangsu
China	General hospital of eastern theater command	Nanjing	Nanjing
China	Affiliated Cancer Hospital of Guangxi Medical University	Nanning	Guangxi
China	The Second Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine	Shanghai	Shanghai
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	The First Affiliated Hospital of Shenzhen University	Shenzhen	Guangdong
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Second Affiliated Hospital of Suzhou University	Suzhou	Jiangsu
China	Tangshan Workers' Hospital	Tangshan	Hebei
China	First Affiliated Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Xijing Hospital, Fourth Military Medical University	Xi'an	Shaanxi
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	People's Hospital of Ningxia Hui Autonomous Region	Yinchuan	Ningxia
China	Zhejiang Cancer Hospital	Zhejiang	Hangzhou
China	Henan Provincial People's Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Peking University First Hospital	Peking University

Country where clinical trial is conducted

China, 

References & Publications (30)

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Kong H, Xu LM, Wang DX. Perioperative neurocognitive disorders: A narrative review focusing on diagnosis, prevention, and treatment. CNS Neurosci Ther. 2022 Aug;28(8):1147-1167. doi: 10.1111/cns.13873. Epub 2022 Jun 1. — View Citation

Lavon H, Matzner P, Benbenishty A, Sorski L, Rossene E, Haldar R, Elbaz E, Cata JP, Gottumukkala V, Ben-Eliyahu S. Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers. Br J Anaesth. 2018 Jan;120(1):188-196. doi: 10.1016/j.bja.2017.11.004. Epub 2017 Nov 23. — View Citation

Li B, Li Y, Tian S, Wang H, Wu H, Zhang A, Gao C. Anti-inflammatory Effects of Perioperative Dexmedetomidine Administered as an Adjunct to General Anesthesia: A Meta-analysis. Sci Rep. 2015 Jul 21;5:12342. doi: 10.1038/srep12342. — View Citation

Li CJ, Wang BJ, Mu DL, Hu J, Guo C, Li XY, Ma D, Wang DX. Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery. Br J Surg. 2020 Jan;107(2):e123-e132. doi: 10.1002/bjs.11354. — View Citation

Li Y, Wang B, Zhang LL, He SF, Hu XW, Wong GT, Zhang Y. Dexmedetomidine Combined with General Anesthesia Provides Similar Intraoperative Stress Response Reduction When Compared with a Combined General and Epidural Anesthetic Technique. Anesth Analg. 2016 Apr;122(4):1202-10. doi: 10.1213/ANE.0000000000001165. — View Citation

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of intensive care unit (ICU) admission after surgery.	Percentage of patients who required ICU admission within 30 days after surgery.	Up to 30 days after surgery.
Other	Intensity of pain after surgery.	Intensity of pain will be assessed with the Numeric Rating Scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain) twice daily during the first 4 postoperative days.	Two hours after surgery and during the first 4 postoperative days.
Other	Subjective sleep quality after surgery.	Subjective sleep quality will be assessed with the Numeric Rating Scale (NRS; an 11-point scale where 0=the best sleep and 10=the worst sleep) once daily during the first 4 postoperative days.	During the first 4 postoperative days.
Other	Length of stay in hospital after surgery.	Length of stay in hospital after surgery.	Up to 30 days after surgery.
Other	Incidence of postoperative complications within 30 days.	Postoperative complications are defined as new-onset medical events other than delirium that are deemed harmful and require therapeutic intervention, that is grade II or higher on the Clavien-Dindo classification.	Up to 30 days after surgery.
Other	Overall survival after surgery	Time interval from index surgery to all-cause death.	Up to 3 years after surgery of the last enrolled patient.
Other	Cancer-specific survival after surgery	Time interval from index surgery to cancer-specific death, with deaths from other causes being censored at the time of death. Cancer-specific death is defined as death fully attributable to the cancer for which the index surgery is performed and usually involves cancer recurrence/metastasis/progression after exclusion of other causes such as stroke and myocardial infarction.	Up to 3 years after surgery of the last enrolled patient.
Other	Event-free survival after surgery	Time interval from index surgery to cancer recurrence/metastasis/progression, new-onset cancer, new-onset serious illness (requiring hospitalization), or all-cause death, whichever comes first.	Up to 3 years after surgery of the last enrolled patient.
Primary	Progression-free survival after surgery	Time interval from index surgery to cancer recurrence/metastasis/progression or all-cause death, whichever comes first.	Up to 3 years after surgery of the last enrolled patient.
Secondary	Incidence of postoperative delirium.	Delirium will be assessed with the 3D-Confusion Assessment Method (3D-CAM) or CAM for the Intensive Care Unit (CAM-ICU) twice daily during the first 4 postoperative days.	During the first 4 postoperative days.
Secondary	Incidence of cognitive dysfunction at 6 months and 1 year postoperatively.	Cognitive function will be assessed with the Telephone Montreal Cognitive Assessment (T-MoCA; scores range from 0 to 22, with higher score indicating better function) before surgery and at 6 months and 12 months after surgery. A T-MoCA score reduction of 1 standard deviation (SD) or more from baseline will be considered occurrence of cognitive dysfunction.	At 6 months and 1 year postoperatively.