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

NCT ID: NCT02950233

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-04
• Study Completion Date: 2019-03-31

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.

Detailed Description

Persistent Post-Surgical Pain (PPSP) after Video Assisted Thoracic Surgery (VATS) lobectomy procedures is an important health problem for which there is no effective method of prevention. NMDA antagonists and steroids can modify pain signaling-sensitization pathways, and inflammatory-immune pathways, and hence can potentially prevent the development of PPSP. These agents have been safely used in thoracic surgeries to obtain many perioperative benefits, without increasing the harmful effects. Since these agents act by different biological mechanisms, it is appropriate to study their effects in a factorial design to increase the trial efficiency. Before conducting a large multicenter trial, we propose to establish the feasibility by carrying out this feasibility trial.

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. Follow-up visit will be conducted in hospital; day 8 and month 2 by a phone call; and in person follow-up visits at 30 days and 3 months post-randomization; for patients who cannot attend in person, a telephone follow up will be done.

Conditions

Pain, Postoperative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NMDA active + Steroid placebo

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.

Group Type: EXPERIMENTAL

NMDA active

Intervention Type: 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 \[following three weeks\]).

Steroid placebo

Intervention Type: 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.

Steroid active + NMDA placebo

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.

Group Type: EXPERIMENTAL

Steroid active

Intervention Type: 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 placebo

Intervention Type: 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 active + Steroid active

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.

Group Type: EXPERIMENTAL

NMDA active

Intervention Type: 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 \[following three weeks\]).

Steroid active

Intervention Type: 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 placebo + Steroid placebo

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.

Group Type: PLACEBO_COMPARATOR

NMDA placebo

Intervention Type: 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 \[following three weeks\]).

Steroid placebo

Intervention Type: 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.

Interventions

NMDA active

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 \[following three weeks\]).

Intervention Type: DRUG

Steroid active

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.

Intervention Type: DRUG

NMDA placebo

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 \[following three weeks\]).

Intervention Type: DRUG

Steroid placebo

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18-75 years of age,
• Planned elective VATS pulmonary lobectomy,
• Provide written informed consent to participate.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Population Health Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

PJ Devereaux, MD, PhD

Role: STUDY_CHAIR

McMaster University

Locations

Cleveland Clinic

Cleveland, Ohio, United States

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 32104059 (View on PubMed)

Other Identifiers

2016-001-PS

Identifier Type: -

Identifier Source: org_study_id