Intraoperative Blood Pressure Management and Dexamethasone in Lung Cancer Surgery

Sponsor

Peking University First Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04209218

Collaborator

(none)

1,988

Enrollment

Location

Arms

79.8

Anticipated Duration (Months)

24.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Surgery is the front-line therapy for non-small cell lung cancer (NSCLC) but postoperative complications remains high and patients' long-term outcome is still challenging. In addition to surgery, anesthetic management particularly intraoperative blood pressure management and use of dexamethasone may affect patients' early and long-term outcomes after surgery for NSCLC. This study aims to investigate the impact of intraoperative blood pressure management and dexamethasone administration on early and long-term outcomes in patients undergoing surgery for lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer Surgery Blood Pressure Management Dexamethasone Overall Survival Postoperative Complications	Drug: Dexamethasone Other: Targeted blood pressure management Drug: Placebo Other: Routine blood presure management	N/A

Detailed Description

Surgical resection is the main treatment for patients with non-small cell lung cancer (NSCLC) and continuous efforts have been made to evolve surgical strategies and techniques. It has been now been realized that perioperative period is characterized with profound changes and anesthesia management may also affect outcomes of patients after cancer surgery.

Even under well controlled conditions, blood pressure fluctuation frequently occurs during anesthesia and surgery. In previous studies, intraoperative hypotension was associated with increased risk of organ injuries (such as delirium, acute kidney injury, myocardial injury, and stroke) and higher 1-year mortality. Unpublished data showed that intraoperative hypotension was also associated with shortened long-term survival in patients after lung cancer surgery. In a recent trial, individualized intraoperative blood pressure management which avoided intraoperative hypotension decreased the incidence of postoperative organ injury when compared with routine practice. Avoiding intraoperative hypotension may also prolong survival after lung cancer surgery. However, evidences are lacking regarding this topic.

Dexamethasone is frequently used for prevention of postoperative nausea and vomiting. Studies showed that a single low-dose dexamethasone has anti-inflammatory effect and can regulate immune function. It has been shown that perioperative dexamethasone can improve analgesia after surgery. In retrospective studies, perioperative low-dose dexamethasone was associated with less wound infection and improved long-term survival in patients after surgeries for pancreatic and lung cancer. It is hypothesized that intraoperative dexamethasone may reduce postoperative complications and improve long-term survival after lung cancer surgery. Interventional studies are required to confirm this hypothesis.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1988 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

A 2 × 2 factorial randomized controlled trialA 2 × 2 factorial randomized controlled trial

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

For dexamethasone administration, all participants, care providers, investigators, and outcomes assessors are masked. For blood pressure management, participants and outcome assessors are masked.

Primary Purpose:

Prevention

Official Title:

Impact of Intraoperative Blood Pressure Management and Dexamethasone on Patient's Outcomes After Lung Cancer Surgery: A 2 × 2 Factorial Randomized Controlled Trial

Actual Study Start Date :

Apr 7, 2020

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Routine blood pressure management + placebo Blood pressure is maintained according to routine practice. Placebo (normal saline 2 ml) is administered before anesthesia induction.	Drug: Placebo Placebo (2 ml normal saline) is administered before anesthesia induction. Other Names: Normal saline Other: Routine blood presure management Blood pressure is maintained according to routine practice.
Experimental: Routine blood pressure management + dexamethasone Blood pressure is maintained according to routine practice. Dexamethasone (10 mg/2 ml) ia administered before anesthesia induction.	Drug: Dexamethasone Dexamethasone (10 mg/2 ml) is administered before anesthesia induction. Other Names: Glucocorticoids Other: Routine blood presure management Blood pressure is maintained according to routine practice.
Experimental: Targeted blood pressure management + placebo Blood pressure is maintained within ±10% from baseline. Placebo (normal saline 2 ml) is administered before anesthesia induction.	Other: Targeted blood pressure management Blood pressure is maintained within ±10% from baseline. Drug: Placebo Placebo (2 ml normal saline) is administered before anesthesia induction. Other Names: Normal saline
Experimental: Targeted blood pressure management + dexamethasone Blood pressure is maintained within ±10% from baseline. Dexamethasone (10 mg/2 ml) is administered before anesthesia induction.	Drug: Dexamethasone Dexamethasone (10 mg/2 ml) is administered before anesthesia induction. Other Names: Glucocorticoids Other: Targeted blood pressure management Blood pressure is maintained within ±10% from baseline.

Outcome Measures

Primary Outcome Measures

Overall survival after surgery [Up to 5 years after surgery]
Overall survival after surgery
Incidence of organ injury and complications within 5 days after surgery (sub-study). [Up to 5 days after surgery.]
Organ injury includes delirium, acute kidney injury and myocardial injury. Postoperative complications are generally defined as newly occurred medical conditions that are harmful to patients' recovery and required therapeutic intervention, i.e., grade II or above on the Clavien-Dindo classification.

Secondary Outcome Measures

Recurrence-free survival after surgery [Up to 5 years after surgery]
Recurrence-free survival after surgery
Cancer-specific survival after surgery [Up to 5 years after surgery]
Cancer-specific survival after surgery
Event-free survival after surgery [Up to 5 years after surgery]
Event-free survival after surgery
Rate of intensive care unit (ICU) admission after surgery (sub-study) [During the day of surgery]
Rate of ICU admission after surgery
Rate of ICU admission with endotracheal intubation after surgery (sub-study) [During the day of surgery]
Rate of ICU admission with endotracheal intubation after surgery
Duration of mechanical ventilation in ICU after surgery (sub-study) [Up to 30 days after surgery]
Duration of mechanical ventilation in ICU after surgery
Length of stay in ICU after surgery (sub-study) [Up to 30 days after surgery]
Length of stay in ICU after surgery
Incidence of organ injury within 5 days after surgery (sub-study) [Up to 5 days after surgery]
Organ injury includes delirium, acute kidney injury and myocardial injury. Delirium is assessed with the 3-minute diagnostic assessment for CAM-defined delirium (3D-CAM). Acute kidney injury is diagnosed according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Myocardial injury is diagnosed according to the serum cardiac troponin I level (higher than upper normal limit of the hospital's clinical laboratory).
Incidence of complications within 30 days after surgery (sub-study) [Up to 30 days after surgery]
Postoperative complications are defined as new-onset medical events that are harmful to patients' recovery and required therapeutic intervention, i.e., grade II or above on the Clavien-Dindo classification.
Length of stay in hospital after surgery (sub-study) [Up to 30 days after surgery]
Length of stay in hospital after surgery
Rate of 30-day all-cause mortality (sub-study) [Up to 30 days after surgery]
Death due to any cause within 30 days after surgery

Other Outcome Measures

Overall survival after surgery in cancer patients [Up to 5 years after surgery]
Overall survival after surgery in cancer patients
Recurrence-free survival after surgery in cancer patients [Up to 5 years after surgery]
Recurrence-free survival after surgery in cancer patients
Cancer-specific survival after surgery in cancer patients [Up to 5 years after surgery]
Cancer-specific survival after surgery in cancer patients
Event-free survival after surgery in cancer patients [Up to 5 years after surgery]
Event-free survival after surgery in cancer patients
30-item quality of life in 1-, 2-, and 3-year survivors [At the end of the 1st, 2nd, and 3rd year after surgery]
Quality of life is assessed with the 30-item Core Quality of Life Questionnaire (QLQ-C30), which assess functioning and symptom scales. The score of each scale ranges from 0 to 100, with higher score indicating better function or worse symptom.
13-item quality of life in 1-, 2-, and 3-year survivors [At the end of the 1st, 2nd, and 3rd year after surgery]
Quality of life is assessed with the 13-item Quality of Life Questionnaire-Lung Cancer Module (QLQ LC-13), which assess symptom scales. The score of each scale ranges from 0 to 100, with higher score indicating worse symptom. The QLQ LC-13 is a supplementary questionnaire module to be employed in conjunction with the QLQ-C30.
Pain score within 3 days after surgery (sub-study) [Up to 3 days after surgery]
Pain score is assessed with the Numeric Rating Scale, an 11-point scale where 0=no pain and 10=the worst pain.
Subjective sleep quality score within 3 days after surgery (sub-study) [Up to 3 days after surgery]
Subjective sleep quality is assessed with the Numeric Rating Scale, an 11-point scale where 0=the best sleep and 10=the worst sleep.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged >50 years but <90 years.
Diagnosed as resectable primary non-small cell lung cancer (stage IA-IIIA) and scheduled for radical surgery with an expected duration of >2 hours.
Agree to participate in this study and sign the informed consent.

Exclusion Criteria:

Clinical examinations suggest non-resectable lung cancer or patients scheduled for a biopsy surgery.
Recurrent or metastatic lung cancer.
History of cancer or complicated with cancer in other organs.
Long-term exposure to glucocorticoids or other immunosuppressant(s) due to autoimmune disease or organ transplantation.
Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg); or requirement of vasopressors to maintain blood pressure.
Persistent atrial fibrillation, or acute cardiovascular events (acute coronary syndrome, stroke, or congestive heart failure) within 3 months.
Severe hepatic dysfunction (Child-Pugh C) or renal failure (requirement of renal replacement therapy).
Any other circumstances considered unsuitable for study participation by attending physicians or investigators.