Preventing pAIn With NMDA Antagonists - Steroids in Thoracoscopic lObectomy Procedures (PAIN-STOP) Pilot Trial

NCT02950233 | Terminated Phase 3 FDA Drug

• 1 other identifier: 2016-001-PS
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 2

Brief Summary

The objective of the PAIN-STOP trial is to assess the feasibility of a larger randomized controlled trial (RCT) evaluating NMDA antagonists and IV steroids, as compared to placebo, in decreasing the chances of clinically significant persistent post-surgical pain (PPSP) after video assisted thoracoscopic surgeries (VATS). This is a multi-centre randomized, controlled clinical trial with a 2 x 2 factorial design. The pilot phase of the trial will recruit 48 patients and follow them for 3 months. Patients will be randomized to one of four groups: 1) NMDA active + Steroid placebo; 2) Steroid active + NMDA placebo; 3) NMDA active + Steroid active; 4) NMDA placebo + Steroid placebo.

Conditions

Pain, Postoperative

Keywords

postoperative pain; VATS; activities of daily living; quality of life

Outcome Measures

Primary Outcomes (3)

• Recruitment

  Ability to recruit 90% of eligible patients.

  6 months

• Recruitment

  Ability to recruit at least 4 patients per month per site, and complete the recruitment over a 6-month period.

  6 months

• Follow-up

  Ability to obtain follow-up in \>90% of enrolled patients, at three months.

  9 months

Secondary Outcomes (9)

• NRS - Incidence of PPSP

  3 months

• NRS - Incidence of PPSP with movement evoked

  3 months

• Rate of change of postoperative pain intensity

  3 months

• Use of narcotic analgesic medication

  3 months

• Presence of NP

  3 months

Other Outcomes (5)

• Incidence of myocardial infarction and injury

  3 months

• Incidence of postoperative pneumonia

  3 months

• Incidence of prolonged air-leak

  3 months

Study Arms (4)

NMDA active + Steroid placebo

EXPERIMENTAL

NMDA active: ketamine (0.5 mg/kg IV bolus pre-incision and 0.1 mg/kg/hr infusion postoperatively up to 24 hours) and oral memantine (5 mg BID \[first week\]; 10 mg BID \[following three weeks\]). Steroid placebo: two doses of normal saline; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.

Drug: NMDA active; Drug: Steroid placebo

Steroid active + NMDA placebo

EXPERIMENTAL

NMDA placebo: normal saline (IV bolus pre-incision and infusion postoperatively up to 24 hours) and oral matching placebo to memantine (one capsule BID \[first week\]; one capsule BID \[following three weeks\]). Steroid active: two doses of dexamethasone; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.

Drug: Steroid active; Drug: NMDA placebo

NMDA active + Steroid active

EXPERIMENTAL

NMDA active: ketamine (0.5 mg/kg IV bolus pre-incision and 0.1 mg/kg/hr infusion postoperatively up to 24 hours) and oral memantine (5 mg BID \[first week\]; 10 mg BID \[following three weeks\]). Steroid active: two doses of dexamethasone; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.

Drug: NMDA active; Drug: Steroid active

NMDA placebo + Steroid placebo

PLACEBO COMPARATOR

NMDA placebo: normal saline (IV bolus pre-incision and infusion postoperatively up to 24 hours) and oral matching placebo to memantine (one capsule BID \[first week\]; one capsule BID \[following three weeks\]). Steroid placebo: two doses of normal saline; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.

Drug: NMDA placebo; Drug: Steroid placebo

Interventions

NMDA active DRUG

NMDA active group will involve ketamine (0.5 mg/kg IV bolus pre-incision and 0.1 mg/kg/hr infusion postoperatively up to 24 hours) and oral memantine (5 mg BID \[first week\]; 10 mg BID \[following three weeks\]).

NMDA active + Steroid active; NMDA active + Steroid placebo

Steroid active DRUG

Steroid active group will involve two doses of dexamethasone; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.

NMDA active + Steroid active; Steroid active + NMDA placebo

NMDA placebo DRUG

NMDA active group will involve normal saline (IV bolus pre-incision and infusion postoperatively up to 24 hours) and oral matching placebo to memantine (1 capsule BID \[first week\]; 1 capsule BID \[following three weeks\]).

NMDA placebo + Steroid placebo; Steroid active + NMDA placebo

Steroid placebo DRUG

Steroid placebo group will involve two doses of normal saline; one dose given prior to starting surgery and one dose given on the morning of second postoperative day.

NMDA active + Steroid placebo; NMDA placebo + Steroid placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age,
• Planned elective VATS pulmonary lobectomy,
• Provide written informed consent to participate.

You may not qualify if:

• Current pain on the same side of the chest of moderate to severe intensity (\>3/10 in 0-10 numerical rating scale (NRS) - where 0=no pain, 10=maximum pain),
• Known intracranial mass or cerebral aneurysm or raised intraocular pressure,
• Severe renal impairment (creatinine clearance based GFR of \<30ml/min),
• Allergies to one or more of the study medications,
• Steroid treatment \> 10mg/day of Prednisolone or its equivalent for \> 3 weeks within the last 3 months,
• History of schizophrenia or bipolar disorder,
• History of drug addiction (prescription or non-prescription drug addiction diagnosed by a physician, excluding alcohol),
• Current diagnosis of Cushing's syndrome,
• Pregnancy,
• Previous participation in the PAIN-STOP trial.

Sponsors & Collaborators

• Population Health Research Institute: lead

Study Sites (2)

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

St. Joseph's Healthcare

Hamilton, Ontario, L8N4A6, Canada

Location

Related Publications (1)

• Shanthanna H, Turan A, Vincent J, Saab R, Shargall Y, O'Hare T, Davis K, Fonguh S, Balasubramaniam K, Paul J, Gilron I, Kehlet H, Sessler DI, Bhandari M, Thabane L, Devereaux PJ. N-Methyl-D-Aspartate Antagonists and Steroids for the Prevention of Persisting Post-Surgical Pain After Thoracoscopic Surgeries: A Randomized Controlled, Factorial Design, International, Multicenter Pilot Trial. J Pain Res. 2020 Feb 12;13:377-387. doi: 10.2147/JPR.S237058. eCollection 2020.

  PMID: 32104059 DERIVED

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

• PJ Devereaux, MD, PhD

  McMaster University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients, health care providers, data collectors, outcome adjudicators, and Investigators (e.g., Steering Committee Members) will all be blind to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We will randomize patients in a 1:1:1:1 fashion to receive; 1) NMDA active + dexamethasone placebo, 2) dexamethasone active + NMDA placebo, 3) NMDA active + dexamethasone active, and 4) NMDA placebo + dexamethasone placebo.

Study Record Dates

• First Submitted: October 28, 2016
• First Posted: November 1, 2016
• Study Start: May 4, 2017
• Primary Completion: December 31, 2018
• Study Completion: March 31, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (1)