Dexmedetomidine Supplemented Analgesia and Long-term Survival After Cancer Surgery

Sponsor

Peking University First Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03012971

Collaborator

Affiliated Hospital of Hebei University (Other), Qingdao Municipal Hospital (Other), The Second Affiliated Hospital of Air Force Medical University (Other), Beijing Chao Yang Hospital (Other), Beijing Shijitan Hospital, Capital Medical University (Other), Beijing Tsinghua Chang Gung Hospital (Other), Peking University International Hospital (Other), Beijing Ditan Hospital (Other), Guizhou Provincial People's Hospital (Other), The Third Xiangya Hospital of Central South University (Other), Shanxi Provincial Cancer Hospital (Other), Tianjin Hospital of ITCWM-Nankai Hospital (Other), Zhongda Hospital Southeast University (Other)

1,500

Enrollment

Location

Arms

86.8

Anticipated Duration (Months)

17.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A majority of the elderly patients undergo surgery for malignant tumors. For these patients, postoperative tumor recurrence and metastasis are main factors that worsen long-term outcomes. The investigators hypothesize that dexmedetomidine supplemented analgesia in elderly patients after cancer surgery may help to maintain immune function and improve long-term outcomes, possibly by relieving stress and inflammatory response, improving analgesic efficacy and sleep quality, and reducing delirium incidence.

Condition or Disease	Intervention/Treatment	Phase
Elderly Surgery Analgesia Dexmedetomidine Long-term Outcome	Drug: Dexmedetomidine supplemented morphine analgesia Drug: Morphine analgesia	N/A

Detailed Description

A majority of the elderly patients undergo surgery for malignant tumors. For these patients, postoperative tumor recurrence and metastasis are main factors that worsen the quality of life and shorten the duration of survival. Perioperative immune function is a key element that influences postoperative tumor recurrence and metastasis; but it is subject to the impacts of many factors. Studies showed that elevated cortisol level and inflammation provoked by surgical stress result in suppression of immune function, whereas dexmedetomidine alleviates the elevated cortisol level and inhibit excessive inflammation; high-dose opioids inhibit the immune function and increase the invasiveness of tumor cells, whereas dexmedetomidine reduces the consumption of opioids during perioperative period; postoperative sleep disturbances also impair immune function, whereas dexmedetomidine improves sleep quality in patients after surgery; occurrence of postoperative delirium is associated with increased mortality, whereas dexmedetomidine reduces delirium incidence. The investigators hypothesize that dexmedetomidine supplemented analgesia in elderly patients after cancer surgery may improve the long-term outcomes, possibly by relieving stress and inflammatory response, improving analgesic efficacy and sleep quality, and reducing delirium incidence.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Impact of Dexmedetomidine Supplemented Analgesia on Long-term Survival in Elderly Patients After Cancer Surgery: a Multicenter Randomized Controlled Trial

Actual Study Start Date :

Jan 6, 2017

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine group Dexmedetomidine supplemented morphine analgesia is provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains a mixture of morphine (0.5 mg/ml) and dexmedetomidine (1.25 ug/ml), diluted with normal saline to a total volume of 160 ml. 5-HT3 receptor antagonist is added when necessary. 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 from 6 to 8 minutes.	Drug: Dexmedetomidine supplemented morphine analgesia Patients in this group receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is a mixture of dexmedetomidine (1.25 ug/ml) and morphine (0.5 mg/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout time from 6 to 8 minutes.
Placebo Comparator: Control group Morphine analgesia is provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains morphine (0.5 mg/ml), diluted with normal saline to a total volume of 160 ml. 5-HT3 receptor antagonist is added when necessary. 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 from 6 to 8 minutes.	Drug: Morphine analgesia Patients in this group receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is morphine (0.5 mg/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout time from 6 to 8 minutes.

Arm

Intervention/Treatment

Experimental: Dexmedetomidine group

Dexmedetomidine supplemented morphine analgesia is provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains a mixture of morphine (0.5 mg/ml) and dexmedetomidine (1.25 ug/ml), diluted with normal saline to a total volume of 160 ml. 5-HT3 receptor antagonist is added when necessary. 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 from 6 to 8 minutes.

Drug: Dexmedetomidine supplemented morphine analgesia

Patients in this group receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is a mixture of dexmedetomidine (1.25 ug/ml) and morphine (0.5 mg/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout time from 6 to 8 minutes.

Placebo Comparator: Control group

Morphine analgesia is provided for patients in this group in the form of patient-controlled intravenous analgesia. The formula contains morphine (0.5 mg/ml), diluted with normal saline to a total volume of 160 ml. 5-HT3 receptor antagonist is added when necessary. 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 from 6 to 8 minutes.

Drug: Morphine analgesia

Patients in this group receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is morphine (0.5 mg/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout time from 6 to 8 minutes.

Outcome Measures

Primary Outcome Measures

Overall survival after surgery [Up to 7 years after surgery]
Overall survival after surgery

Secondary Outcome Measures

Recurrence-free after surgery [Up to 7 years after surgery]
Recurrence-free after surgery
Cancer-specific survival after surgery [Up to 7 years after surgery]
Cancer-specific survival after surgery
Event-free survival after surgery [Up to 7 years after surgery]
Event-free survival after surgery
Cognitive function of survival patients at 2 years after surgery [At the end of 2 years after surgery]
Cognitive function was assessed with Telephone Interview for Cognitive Function-Modified (TICS-M)
Quality of life of survival patients at 2 years after surgery [At the end of 2 years after surgery]
Quality of life was assessed with World Health Organization Quality of Life-Bref (WHOQOL-BREF)

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age >= 65 years, < 90 years;
Scheduled to undergo surgery for primary solid organ cancer under general anesthesia, with an expected duration of surgery >=2 hours;
Planned to use patient-controlled intravenous analgesia after surgery;
Provide written informed consent.

Exclusion Criteria:

Preoperative history of schizophrenia, epilepsy, parkinsonism or myasthenia gravis;
Preoperative radio- or chemotherapy;
Inability to communicate in the preoperative period because of coma, profound dementia or language barrier;
Preoperative obstructive sleep apnea (previously diagnosed as obstructive sleep apnea, or a STOP-Bang score >= 3);
Brain trauma or neurosurgery;
Preoperative left ventricular ejection fraction < 30%, sick sinus syndrome, severe sinus bradycardia (< 50 beats per minute), or second-degree or above atrioventricular block without pacemaker;
Severe hepatic dysfunction (Child-Pugh class C) or severe renal dysfunction (requirement of renal replacement therapy before surgery);
ASA classification >= IV.