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

Pain, Postoperative Clinical Trial

— PAIN-STOP  

Official title:

NMDA Antagonists and Steroids for the Prevention of Persisting Post-Surgical Pain After Thoracoscopic Surgeries: A Randomized Controlled, Factorial Design, International, Multicentre Pilot Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02950233
• Other study ID #: 2016-001-PS
• Status: Terminated
• Phase: Phase 3
• Start date: May 4, 2017
• Est. completion date: March 31, 2019

Study information

• Verified date: January 2020
• Source: Population Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: March 31, 2019
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pain, Postoperative

Intervention

Drug:
• 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]).
• 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.
• 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]).
• 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.

Locations

Country	Name	City	State
Canada	St. Joseph's Healthcare	Hamilton	Ontario
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Population Health Research Institute

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of myocardial infarction and injury	Incidence of myocardial infarction and myocardial injury after noncardiac surgery (MINS)	3 months
Other	Incidence of postoperative pneumonia	Incidence of postoperative pneumonia	3 months
Other	Incidence of prolonged air-leak	Incidence of prolonged air-leak	3 months
Other	Incidence of new intubation and positive pressure ventilation	Incidence of new intubation and positive pressure ventilation	3 months
Other	Incidence of surgical site infection	Incidence of surgical site infection	3 months
Primary	Recruitment	Ability to recruit 90% of eligible patients.	6 months
Primary	Recruitment	Ability to recruit at least 4 patients per month per site, and complete the recruitment over a 6-month period.	6 months
Primary	Follow-up	Ability to obtain follow-up in >90% of enrolled patients, at three months.	9 months
Secondary	NRS - Incidence of PPSP	Intensity of PPSP on a scale of 0-10, at 3 months after randomization [0-10 numerical rating scale (NRS) - where 0=no pain, 10=maximum pain].	3 months
Secondary	NRS - Incidence of PPSP with movement evoked	Incidence of PPSP (in and/or around the surgical scar) at 3 months after randomization, as the presence of movement evoked pain > 3/10 in 0-10 NRS.	3 months
Secondary	Rate of change of postoperative pain intensity	The rate of change of postoperative pain intensity measured over time (pain trajectory).	3 months
Secondary	Use of narcotic analgesic medication	Use of narcotic analgesic medication > 3 days/week beyond 4 weeks and up to 3 months after randomization.	3 months
Secondary	Presence of NP	Presence of NP as > 3 out 7 items using DN4 scale, at measured at 3 months after randomization.	3 months
Secondary	BPI score	Difference in interference with activities of daily living measured using Brief Pain Inventory interference score, measured at 3 months after randomization.	3 months
Secondary	Thoracic surgery specific activity limitations	Difference in thoracic surgery specific activity limitations, measured at 3 months after randomization.	3 months
Secondary	Change in global health status	Change in global health status measured using global impression of change (GIC) scale at 3 months after randomization.	3 months
Secondary	Difference in Quality of Life	Difference in Quality of Life (QoL) using European Organization for Research and Treatment of Cancer (EORTC) QoL-30 at 3 months after randomization.	3 months