Preoperative Oral Midazolam to Postoperative Pain Relief in Sleep Disturbance or Anxiety Patients With Colorectal Cancer

NCT ID: NCT06407518

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-24
• Study Completion Date: 2025-12-31

Brief Summary

Previous studies have indicated a high incidence of sleep disturbances and anxiety symptoms in individuals with colorectal cancers prior to undergoing surgery, leading to worsened postoperative pain, slower recovery, and higher risk of chronic pain. The enhancement of sleep quality is intricately linked to reducing stress. Preoperative drugs that combine hypnosis and anti-anxiety have not been studied in colorectal cancer patients. Midazolam oral solution is safe and effective for short-term hypnotic and anti-anxiety effects in clinical preoperative settings. In the current randomized controlled clinical trial, 280 patients experiencing sleep disturbance or anxiety prior to colorectal cancer surgery will receive midazolam solution to assess its potential efficacy in reducing postoperative pain, expediting recovery, and decreasing the likelihood of chronic pain. Additionally, the study aims to explore the potential connections between midazolam administration and reductions in stress and inflammation.

Detailed Description

Preoperative sleep disturbance and anxiety worsen postoperative pain for patients undergoing surgeries. Research indicates that a significant proportion of patients, ranging from 8.8% to 79.1%, experience disturbances in sleep or anxiety prior to surgery. These preoperative issues have been shown to have lasting and intricate effects on postoperative pain, fatigue, and depression. Therefore, it is imperative for clinical doctors to promptly identify preoperative sleep disturbances and anxiety in order to offer appropriate support to patients.

Colorectal cancer is the fifth leading cause of death in China, with nearly 40% of patients experiencing insomnia before surgery, consistent with our previous studies. A case-control study demonstrated a protective association between improved sleep quality and relief of postoperative pain in colorectal cancers. Furthermore, individuals undergoing laparoscopic colorectal surgery showed a higher likelihood of experiencing visceral pain compared to somatic pain. Acute visceral pain has the potential to progress into chronic visceral pain, resulting in behavioral manifestations such as anxiety, fear, and depression, which may persist and exacerbate into enduring chronic pain, ultimately impacting the individual's quality of life. Currently, studies have shown that disturbed preoperative sleep has become a significant predictor of both acute and chronic postoperative pain. Therefore, finding effective interventions to promote preoperative sleep is a continuing consideration for clinicians.

Pharmacological intervention is the primary approach for preoperative sleep disturbances or anxiety. Finding appropriate drug is a challenge that needs to be solved in the clinical practice. There is currently a lack of evidence-based medical guidelines regarding pharmacologic interventions for preoperative sleep disturbances and anxiety. Research has indicated that zolpidem can enhance sleep quality in patients prior to surgery, decrease the need for analgesics during the procedure, and alleviate postoperative pain. Nevertheless, there is a demand for agents that possess both short-term hypnotic and anxiolytic properties, whereas zolpidem solely exhibits hypnotic effects. Midazolam, a short-acting benzodiazepine, is often used before anesthesia for its short-term hypnotic and anxiolytic effects. Studies have found that midazolam oral solution is safe and effective for short-term use in clinical pre-surgical settings. There are no studies on using oral midazolam solution to improve sleep and reduce anxiety in colorectal cancer patients before surgery. Our previous research found that a dose of 7.2mg can effectively induce sleep with minimal side effects in 50% patients before surgery.

In summary, the present study intends to carry out a prospective,randomized,double-blind,placebo-controlled clinical study to investigate the hypothesis that preoperative oral midazolam solution could reduce acute postoperative pain, promote early recovery, and reduce the risk of chronic pain in patients with poor sleep or anxiety before colorectal cancer surgery. It is postulated that the potential benefits of preoperative oral midazolam solution may be attributed to decreased stress levels, and lowered inflammation markers.

Conditions

Preoperative; Sleep Disturbance; Anxiety; Midazolam; Pain, Postoperative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Midazolam oral solution Group

The intervention drug is midazolam oral solution at a dose of 7-10mg. The starting dosage is 7mg, with subsequent individual increases of 1mg up to a maximum dose of 10mg if patients do not achieve sleep within 30 minutes of administration. The individual dose wil be consistently maintained at the corresponding level every night until the surgery.

Group Type: EXPERIMENTAL

Midazolam oral solution

Intervention Type: DRUG

Each individual administers the midazolam oral solution nightly from enrollment to the surgry.

Control Group

Placebo is a solution of midazolam oral solution that looks, tastes, and appears the same as the intervention drug, similar to the experimental group increment method.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Each individual administers placebo solution nightly from enrollment to the surgry.

Interventions

Midazolam oral solution

Each individual administers the midazolam oral solution nightly from enrollment to the surgry.

Intervention Type: DRUG

Placebo

Each individual administers placebo solution nightly from enrollment to the surgry.

Intervention Type: OTHER

Other Intervention Names

Midazolam oral solution, YICHANG HUMANWELL PHARMACEUTICAL

Eligibility Criteria

Inclusion Criteria

• 1. Signed of informed consent voluntarily; 2. Native Chinese speaker; 3. Age 18-60 years old, male or female; 4. BMI 18-30 kg/m2; 5. American Society of Anesthesiologists (ASA) grade 1 or 2, New York Heart Association (NYHA) gradeⅠor Ⅱ; 6. Non-emergency laparoscopic colorectal cancer resection; 7. General anesthesia with tracheal intubation; 8. Sleep disturbance (the Insomnia Severity Index,ISI≥15 ) or Anxiety (Generalized Anxiety Disorder scale-7,GAD-7≥10 ) from admission to surgery.

Exclusion Criteria

• 1. Contraindications for Midazolam Oral Solution (According to the Instruction for Midazolam Oral Solution); 2. High risk of Obstructive Sleep Apnea Symptoms (Total score of STOP-Bang scale ≥3 points); 3. Suspected dementia (Total score of Mini-Mental State Examination (MMSE) according to years of education: 0 year≤19 points; 1~6 years≤22 points; above of 6 years≤26 points); 4. Severe depressive symptom within two weeks (Total score of Patient Health Questionnaire-9 (PHQ-9)≥15); 5. History of Neurological and Psychiatric diseases (According to the electronic medical record system); 6. History of Chronic Obstructive Pulmonary Disease (According to the electronic medical record system); 7. History of Heart Failure (According to the electronic medical record system); 8. Intestinal obstruction(The electronic medical record system records those who currently have any type of intestinal obstruction); 9. Liver and renal insufficiency; 10. Have taken opioids or drugs that act on the central nervous system within one week; 11. Take CYP3A4 isoenzyme inhibitors or inducers within one week (According to the Instruction for Midazolam Oral Solution); 12. Consume any alcoholic beverage within 24 hours; 13. Substance abusers (including alcohol, drugs or addictive substances); 14. Pregnant or lactating women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sixth Affiliated Hospital, Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

SanQing Jin

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

sanqing Jin, MD

Role: PRINCIPAL_INVESTIGATOR

The Sixth Affiliated Hospital, Sun Yat-sen University

Locations

the Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Sanqing Jin, MD

Role: CONTACT

jinsq@mail.sysu.edu.cn

0086-13719366863

Yan Zhou, MD

Role: CONTACT

zhouyan8@mail3.sysu.edu.cn

0086-13632404420

Facility Contacts

SanQing Jin, MD

Role: primary

jinsq@mail.sysu.edu.cn

0086-13719366863

Other Identifiers

2024ZSLYEC-351

Identifier Type: -

Identifier Source: org_study_id