Influence of Aging on Perioperative Methadone Dosing

NCT04526236 | Completed Phase 4 DMC

• 1 other identifier: 190510001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Increasingly, elderly patients undergo anesthesia and surgery. Methadone is a great opioid for perioperative pain management, however, to date there are no pharmacokinetic or pharmacodynamic studies that asses a methadone dose adjustment in the elderly patient. The present study is aimed to characterize the pharmacokinetic and pharmacodynamic age-related changes of methadone in the adult population and further to design reference dosing protocols for intraoperative methadone use according to patient age.

Conditions

Pain, Postoperative; Opioid Use; Methadone Overdose of Undetermined Intent

Keywords

Methadone; Elderly; Postoperative Pain

Outcome Measures

Primary Outcomes (1)

• Methadone plasmatic levels Measured by high pressure liquid chromatography

  Five venous blood samples will be taken from each patient for methadone plasmatic level analysis. Patients will be randomly divided into two groups with different sample collection times. Group 1 at 0.05, 0.75, 1.5, 6, 18 hours post drug administration and Group 2 at 0.25, 1, 3, 12 and 24 hours.

  From the first dose up to 24 hours.

Secondary Outcomes (11)

• Hemodynamics

  Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs. Then, from the entrance to the recovery room every 30 minutes up to 180 minutes.

• Heart Rate

  Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs. Then, from the entrance to the recovery room every 30 minutes up to 180 minutes.

• Pulse oximetry

  Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs. Then, from the entrance to the recovery room every 30 minutes up to 180 minutes.

• BIS

  Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.

• Respiratory rate

  Every 30 minutes. Since entering the recovery room up to 180 mins.

Other Outcomes (4)

• Body fat

  Once, before the anesthetic induction in the operating toom.

• Level of satisfaction with pain management: 10-point scale

  Since the admission to the recovery room up to 2 hours.

• Lean Mass

  Once, before the anesthetic induction in the operating toom.

Study Arms (4)

Methadone 0

PLACEBO COMPARATOR

Induction will be performed with a bolus of propofol, continuous infusion of remifentanil, and rocuronium. Once the patient is intubated and has hemodynamic stability will be administered the placebo drug.

Drug: Methadone Injectable Product

Methadone 1

EXPERIMENTAL

Induction will be performed with a bolus of propofol, continuous infusion of remifentanil, and rocuronium. Once the patient is intubated and has hemodynamic stability will be administered an intravenous methadone dose of 0.05 mg/kg.

Drug: Methadone Injectable Product

Methadone 2

EXPERIMENTAL

Induction will be performed with a bolus of propofol, continuous infusion of remifentanil, and rocuronium. Once the patient is intubated and has hemodynamic stability will be administered an intravenous methadone dose of 0.1 mg/kg.

Drug: Methadone Injectable Product

Methadone 3

EXPERIMENTAL

Induction will be performed with a bolus of propofol, continuous infusion of remifentanil, and rocuronium. Once the patient is intubated and has hemodynamic stability will be administered an intravenous methadone dose of 0.2 mg/kg.

Drug: Methadone Injectable Product

Interventions

Methadone Injectable Product DRUG

Perioperative use of placebo for pain management and remifentanil during the surgery.

Also known as: Methadone 0, Methadone 1 0,05 mg/kg, Methadone 2 0,1 mg/kg, Methadone 3 0,2 mg/kg

Methadone 0; Methadone 1; Methadone 2; Methadone 3

Eligibility Criteria

• Age: 18 Years - 105 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over 18 years.
• ASA I, II or III.
• Laparoscopic Abdominal Surgery.

You may not qualify if:

• BMI\> 35
• Use of opioids up to 5 days before surgery.
• Acute Liver Failure or Chronic Liver Damage Child C.
• Kidney damage with creatinine clearance estimated by Cockcroft-Gault formula \<60 ml/min.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Católica de Chile

Santiago, Santiago Metropolitan, 8320000, Chile

Location

Related Publications (11)

• Sadean MR, Glass PS. Pharmacokinetics in the elderly. Best Pract Res Clin Anaesthesiol. 2003 Jun;17(2):191-205. doi: 10.1016/s1521-6896(03)00002-8.

  PMID: 12817914 BACKGROUND

• Shafer SL. The pharmacology of anesthetic drugs in elderly patients. Anesthesiol Clin North Am. 2000 Mar;18(1):1-29, v. doi: 10.1016/s0889-8537(05)70146-2.

  PMID: 10934997 BACKGROUND

• Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, Billard V, Hoke JF, Moore KH, Hermann DJ, Muir KT, Mandema JW, Shafer SL. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology. 1997 Jan;86(1):10-23. doi: 10.1097/00000542-199701000-00004.

  PMID: 9009935 BACKGROUND

• Schnider TW, Minto CF, Shafer SL, Gambus PL, Andresen C, Goodale DB, Youngs EJ. The influence of age on propofol pharmacodynamics. Anesthesiology. 1999 Jun;90(6):1502-16. doi: 10.1097/00000542-199906000-00003.

  PMID: 10360845 BACKGROUND

• Hilmer SN, McLachlan AJ, Le Couteur DG. Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol. 2007 Jun;21(3):217-30. doi: 10.1111/j.1472-8206.2007.00473.x.

  PMID: 17521291 BACKGROUND

• Kaiko RF, Wallenstein SL, Rogers AG, Grabinski PY, Houde RW. Narcotics in the elderly. Med Clin North Am. 1982 Sep;66(5):1079-89. doi: 10.1016/s0025-7125(16)31383-9. No abstract available.

  PMID: 7132470 BACKGROUND

• Singleton MA, Rosen JI, Fisher DM. Pharmacokinetics of fentanyl in the elderly. Br J Anaesth. 1988 May;60(6):619-22. doi: 10.1093/bja/60.6.619.

  PMID: 3377944 BACKGROUND

• Scott JC, Ponganis KV, Stanski DR. EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil. Anesthesiology. 1985 Mar;62(3):234-41. doi: 10.1097/00000542-198503000-00005.

  PMID: 3919613 BACKGROUND

• Gallagher R. Methadone: an effective, safe drug of first choice for pain management in frail older adults. Pain Med. 2009 Mar;10(2):319-26. doi: 10.1111/j.1526-4637.2008.00551.x. Epub 2009 Jan 16.

  PMID: 19207240 BACKGROUND

• Lugo RA, Satterfield KL, Kern SE. Pharmacokinetics of methadone. J Pain Palliat Care Pharmacother. 2005;19(4):13-24.

  PMID: 16431829 BACKGROUND

• Gagnon B, Almahrezi A, Schreier G. Methadone in the treatment of neuropathic pain. Pain Res Manag. 2003 Fall;8(3):149-54. doi: 10.1155/2003/236718.

  PMID: 14657982 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Maria F Elgueta, MD

  Associate Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The masking will be generated on a research laboratory computer and will be stored in an encrypted file. This information will be known exclusively to a member of the research team present during the surgery, who will hand over preparing the corresponding medicine in a 20 cc syringe and hand it over to the treating anesthesiologist.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomly divided into four groups according to the dose of intravenous methadone to be administered during anesthetic induction, for a total number of 60 patients.

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 25, 2020
• Study Start: September 3, 2019
• Primary Completion: July 13, 2022
• Study Completion: July 13, 2022
• Last Updated: December 21, 2023

Record last verified: 2023-12

Locations

CL (1)