Precision Analgesia for Cardiac Surgery

Analgesia Clinical Trial

Official title:

Precision Perioperative Methadone Use in Adult Cardiac Surgical Patients to Reduce Opioid Use Adverse Effects While Improving Analgesia and Outcomes

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05612399
• Other study ID #: STUDY22060101
• Status: Not yet recruiting
• Start date: April 1, 2025
• Est. completion date: December 1, 2026

Study information

• Verified date: May 2024
• Source: University of Pittsburgh
• Contact: Alisha Maslanka, BS, CCRC
• Phone: 412-864-6779
• Email: maslankaaa[@]upmc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The proposed research is an important extension of an ongoing perioperative personalized analgesia and intravenous opioid pharmacogenetic research. This research focuses on two of the most commonly used oral opioid analgesics, oxycodone, and methadone in elderly adults undergoing cardiac surgery.

Description:

Cardiac surgery patients often experience significant acute postoperative pain, and untreated or undertreated pain has consequences. Each year, 900,000 painful cardiac surgeries occur in the US alone. Pain associated with cardiac surgery results from surgical incision, sternal retraction, internal mammary artery harvesting, saphenous vein removal, placement of mediastinal and chest drains, sternal wires, and release of pro-inflammatory mediators after tissue injury. One study reported that 49%, 62%, and 78% of patients reported severe pain at rest, movement, and coughing, respectively after coronary artery bypass surgery (CABG). Another study showed that 61.4% of patients undergoing cardiac surgery reported moderate to severe pain. Inadequate pain treatment is common in cardiac surgery due to health care providers' fears of causing cardiorespiratory compromise. Poor pain control can trigger sympathoadrenal responses leading to cardiac arrhythmias and myocardial ischemia, restrict mobility to cause venous thrombosis, impair clearance of secretions leading to pulmonary complications such as atelectasis and pneumonia, decrease patient satisfaction and predispose to the development of chronic, persistent surgical pain (CPSP). Improving clinical practice by shifting paradigms: Our research is transformative and will evolve current reactive clinical practice towards proactive precision methods based on genetic risks for surgical pain and ORADE in elderly vulnerable population. This is the first effort to move in the direction of personalizing perioperative opioid use with precise dosing to improve safety and efficacy in cardiac surgery. Preoperative genotyping-based clinical decisions are expected to support clinical implementation in real-world settings. Importantly, investigators will be able to reach beyond the current best-in-class outcomes with precision multi-dose methadone analgesia based on proactive genetic risk identification to maximize safety and efficacy of opioids in all cardiac surgical patients and positively impact socio-economic outcomes in the future. By addressing these critical barriers, this research will help physicians identify patients at risk and improve the safety and efficacy of opioids and surgical pain management while preventing OD, misuse, overdose, and deaths.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: December 1, 2026
• Est. primary completion date: December 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 110 Years

Eligibility

Inclusion Criteria:

• Elderly cardiac surgical patients over 60 years of age

Exclusion Criteria:

• Methadone allergy
• Morbid obesity (BMI >40kg/cm2)
• Severe sleep apnea
• Severe pulmonary disease requiring oxygen therapy
• Preoperative mechanical circulatory support
• Emergency surgery
• Liver disease (liver enzymes more than two times normal)
• End-stage renal disease requiring dialysis
• Serum creatinine more than 2.0mg

Related Conditions & MeSH terms

• Analgesia
• Cardiac Surgery

Locations

Country	Name	City	State
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Kathirvel Subramaniam

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine Genetic Factors - Opioid Related Adverse Events (RD)	Respiratory depression will be measured with binary yes/no responses obtained either via self-report from the patient or reported by the clinical care staff.	Immediately post-surgery during hospital stay
Primary	Determine Genetic Factors - Opioid Related Adverse Events (PONV)	Post-operative nausea and vomiting will be measured with binary yes/no responses obtained either via self-report from the patient or reported by the clinical care staff.	Immediately post-surgery during hospital stay
Primary	Determine Genetic Factors - Opioid Related Adverse Events (Excessive Sedation)	Excessive sedation will be measured with binary yes/no responses obtained either via self-report from the patient or reported by the clinical care staff.	Immediately post-surgery during hospital stay
Primary	Determine Genetic Factors - Uncontrolled severe pain	We postulate that specific CYP2B6, ABCB1, OPRM1, FAAH, and ORM1 genetic variants identify patients at risk for poor pain relief and ORADE with methadone in the immediate post-surgical period. Pain will be measured by the Numerical Rating Scale (NRS) in which 0 = no pain at all and 10 = worst pain imaginable. This will be self-reported responses by the patient.	Immediately post-surgery during hospital stay
Secondary	Opioid use post-operatively	Opioid usage will be recorded via SOAPP-R, a 24-item validated opioid assessment. A score of 18 or higher is considered positive.	POD 5 to 6-months post-operative
Secondary	Patient-Reported Outcomes Measurement Information System	The PROMIS-29 v2.0 will be collected for this outcome measure. The PROMIS survey is scored by the following T-Score Cut Points: 20-55 = better health, 55-60 = mild, 61-69 = moderate, and 71+ = worse health. The general population mean = 50 (SD = 10).	POD 5 to 6-months post-operative
Secondary	Incidence of Chronic Persistent Surgical Pain (CPSP)	CPSP will be obtained via patient-self report as yes/no responses for follow-up assessments. This measure will be reported as mean(SD) for positive CPSP subjects.	POD 5 to 6-months post-operative