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

Population Health Research Institute (PHRI)

Status and phase: Terminated; Phase 3

Conditions: Pain, Postoperative

Treatments: Drug: NMDA active; Drug: Steroid active; Drug: Steroid placebo; Drug: NMDA placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02950233

2016-001-PS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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27 participants in 4 patient groups, including a placebo group

NMDA active + Steroid placebo

Experimental group

Description:

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.

Treatment:

Drug: Steroid placebo

Drug: NMDA active

Steroid active + NMDA placebo

Experimental group

Description:

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.

Treatment:

Drug: Steroid active

Drug: NMDA placebo

NMDA active + Steroid active

Experimental group

Description:

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.

Treatment:

Drug: Steroid active

Drug: NMDA active

NMDA placebo + Steroid placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Steroid placebo

Drug: NMDA placebo