Clinical trial NCT02950233: Preventing pAIn With NMDA Antagonists - Steroids in Thoracoscopic lObectomy Procedures (PAIN-STOP) Pilot Trial
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pain, Postoperative
Keywords: postoperative pain
VATS
activities of daily living
quality of life
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2016-11-01
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Recruitment
timeFrame: 6 months
measure: Recruitment
timeFrame: 6 months
measure: Follow-up
timeFrame: 9 months
Secondary outcomes:
measure: NRS - Incidence of PPSP
timeFrame: 3 months
measure: NRS - Incidence of PPSP with movement evoked
timeFrame: 3 months
measure: Rate of change of postoperative pain intensity
timeFrame: 3 months
measure: Use of narcotic analgesic medication
timeFrame: 3 months
measure: Presence of NP
timeFrame: 3 months
measure: BPI score
timeFrame: 3 months
measure: Thoracic surgery specific activity limitations
timeFrame: 3 months
measure: Change in global health status
timeFrame: 3 months
measure: Difference in Quality of Life
timeFrame: 3 months
Other outcomes:
measure: Incidence of myocardial infarction and injury
timeFrame: 3 months
measure: Incidence of postoperative pneumonia
timeFrame: 3 months
measure: Incidence of prolonged air-leak
timeFrame: 3 months
measure: Incidence of new intubation and positive pressure ventilation
timeFrame: 3 months
measure: Incidence of surgical site infection
timeFrame: 3 months
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
Study officials:
affiliation: McMaster University
name: PJ Devereaux, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.