Clinical trial NCT03200600: Dexamethasone, Flurbiprofen Axetil and Delirium After Lung Cancer Surgery
Official title: Impact of Perioperative Dexamethasone and Flurbiprofen Axetil on Delirium After Surgery for Non-small Cell Lung Cancer: A 2x2 Factorial Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Carcinoma, Non-Small-Cell Lung
Surgery--Complications
Dexamethasone
Flubiprofen Axetil
Delirium
Keywords: Carcinoma, Non-Small-Cell Lung
Surgery
Dexamethasone
Flubiprofen Axetil
Delirium
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
First posted: 2017-06-27
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: Delirium is a common complication in elderly patients after surgery. And its occurrence is associated with worse outcomes. The causes of delirium are multifactorial but may include pain, stress response and inflammation. Dexamethasone is commonly used to prevent the occurrence of postoperative nausea and vomiting. In a randomized controlled trial, small-dose dexamethasone (8 mg) administered before anesthesia induction improved the quality of recovery in patients after cardiac surgery. Flurbiprofen axetil is commonly used to improve postoperative analgesia while decreasing the requirement of opioids. In a randomized trial of the investigators, combined use of flurbiprofen axetil with sufentanil for postoperative analgesia reduced delirium in elderly patients after orthopedic surgery. The purpose of this 2 plus 2 factorial randomized controlled trial is to test the hypothesis that combined use of dexamethasone and flurbiprofen axetil may reduce delirium in elderly patients after lung cancer surgery.

Detailed description: Delirium is an acutely occurred, transient and fluctuating central nervous system dysfunction which is characterized by cognitive dysfunction, decreased level of consciousness, decentralized attention, and/or disturbed perception. It is a common complication in elderly patients after surgery. Systematic reviews showed that 5% to 54.4% of patients developed delirium after noncardiac surgery, and the incidences increase with age.

The development of postoperative delirium is associated with worse outcomes. For example, patients with delirium had increased postoperative complications, prolonged hospital stay, and increased in-hospital mortality; they also had worse long-term outcomes, including declined cognitive function, decreased quality of life, and increased post-hospital mortality.

The causes of delirium are multifactorial and may include pain, stress response and inflammation. Studies showed that postoperative pain is an important risk factor of delirium, whereas good postoperative analgesia reduces the incidence of delirium. Furthermore, the studies found that surgery related inflammatory response also plays an important role in the development of delirium. However, measures that can effectively prevent the occurrence of postoperative delirium are still lacking.

Dexamethasone is commonly used to prevent the occurrence of postoperative nausea and vomiting. In a randomized controlled trial, small-dose dexamethasone (8 mg) administered before anesthesia induction improved the quality of recovery in patients after cardiac surgery. Flurbiprofen axetil is commonly used to improve postoperative analgesia while decreasing the requirement of opioids. In a randomized trial of the investigators, combined use of flurbiprofen axetil with sufentanil for postoperative analgesia reduced delirium in elderly patients after orthopedic surgery.

The purpose of this 2 plus 2 factorial randomized controlled trial is to test the hypothesis that combined use of dexamethasone and flurbiprofen axetil may reduce delirium in elderly patients after lung cancer surgery.

Eligibility criteria: Inclusion Criteria:

1. Age from 18 to 85 years old;
2. Diagnose as non-small-cell lung cancer (stage IA-IIIA);
3. Plan to undergo surgical resection;
4. Provide written informed consents.

Exclusion Criteria:

1. Clinical evidences suggest remote metastasis of the primary cancer; have received radiotherapy, chemotherapy or targeted therapy before surgery; have received previous surgery for lung cancer; diagnosed with other cancer (other than lung cancer) currently or previously;
2. History of therapy with glucocorticoids or immunosuppressants within 1 year, or therapy with non-steroidal anti-inflammatory drugs (NSAIDs) within 1 month;
3. Allergy to glucocorticoids or NSAIDs;
4. Contraindications to dexamethasone or flurbiprofen axetil, such as asthma or hives urticaria induced by aspirin or other NSAIDs; active digestive tract ulcer or bleeding, or history of repeated digestive tract ulcer or bleeding; coagulopathy (platelet count \< 50\*10\^9/L, International Normalized Ratio \> 1.4, or activated partial thromboplastin time \> 4 seconds above upper limit); current therapy with lomefloxacin, norfloxacin, or enoxacin; severe cardiac dysfunction (New York heart association class 3 or above, or Left Ventricular Ejection Fraction less than 30%) or myocardial infarction within 3 months; liver injury (transaminase higher than 2 times of upper limit); kidney injury (creatinine higher than 1.5 times of upper limit); uncontrolled severe hypertension before surgery (\> 180/120 mmHg);
5. American Society of Anesthesiologists (ASA) physical status class IV or higher;
6. Refuse to use patient-controlled analgesia pump after surgery;
7. Other conditions that are considered unsuitable for study participation.

Primary outcomes:
measure: Incidence of delirium during the first five postoperative days.
timeFrame: From postoperative day 1 to postoperative day 5.
Secondary outcomes:
measure: Daily prevalence of delirium during the first five days after surgery.
timeFrame: From postoperative day 1 to postoperative day 5.
measure: Length of stay in hospital after surgery.
timeFrame: From end of surgery until hospital discharge or 30 days after surgery.
measure: Incidence of postoperative complications within 30 days after surgery.
timeFrame: From end of surgery until 30 days after surgery.
measure: All-cause mortality within 30 days after surgery.
timeFrame: From end of surgery until 30 days after surgery.
measure: Cognitive function at 30 days after surgery.
timeFrame: At 30 days after surgery.
measure: Quality of life at 30 days after surgery.
timeFrame: At 30 days after surgery.
Other outcomes:
measure: Richmond agitation sedation scale.
timeFrame: From postoperative day 1 to postoperative day 5.
measure: Severity of pain.
timeFrame: From postoperative day 1 to postoperative day 5.
measure: Cumulative analgesics consumption.
timeFrame: Until postoperative day 3.
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital
name: Dong-xin Wang, Wang
role: PRINCIPAL_INVESTIGATOR
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