Pain, PostoperativePhase 3PAIN-STOPNCT02950233
Preventing pAIn With NMDA Antagonists - Steroids in Thoracoscopic lObectomy Procedures (PAIN-STOP) Pilot Trial
A Phase 3 study testing NMDA active and Steroid active in people with Pain, Postoperative, run by Population Health Research Institute at 2 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pain, Postoperative
- What is being tested?
- NMDA active and Steroid active
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 4 May 2017to 31 Mar 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-75 years of age,
- Planned elective VATS pulmonary lobectomy,
- Provide written informed consent to participate.
Who cannot join
- 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,
Show all 10Show fewer
- 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 locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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.
Read the 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
- Being tested
- NMDA active, Steroid active, NMDA placebo, Steroid placebo
- Keywords
- postoperative pain, VATS, activities of daily living, quality of life
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMDA activeDrug
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 activeDrug
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 placeboDrug
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 placeboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: NMDA placebo; Drug: Steroid placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment
Ability to recruit 90% of eligible patients.
Measured: 6 months
Recruitment
Ability to recruit at least 4 patients per month per site, and complete the recruitment over a 6-month period.
Measured: 6 months
Follow-up
Ability to obtain follow-up in >90% of enrolled patients, at three months.
Measured: 9 months
Secondary outcomes (9)
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].
Measured: 3 months
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.
Measured: 3 months
Rate of change of postoperative pain intensity
The rate of change of postoperative pain intensity measured over time (pain trajectory).
Measured: 3 months
Use of narcotic analgesic medication
Use of narcotic analgesic medication > 3 days/week beyond 4 weeks and up to 3 months after randomization.
Measured: 3 months
Presence of NP
Presence of NP as > 3 out 7 items using DN4 scale, at measured at 3 months after randomization.
Measured: 3 months
BPI score
Difference in interference with activities of daily living measured using Brief Pain Inventory interference score, measured at 3 months after randomization.
Measured: 3 months
Thoracic surgery specific activity limitations
Difference in thoracic surgery specific activity limitations, measured at 3 months after randomization.
Measured: 3 months
Change in global health status
Change in global health status measured using global impression of change (GIC) scale at 3 months after randomization.
Measured: 3 months
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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2016 (estimated)
- Study start4 May 2017
- Primary completion31 Dec 2018
- Study completion31 Mar 2019
Why it stopped: Recruitment was slower than expected and study drug reached expiry
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Population Health Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- PJ Devereaux, MD, PhD, Study chair, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02950233
- Sponsor's protocol ID
- 2016-001-PS
- Acronym
- PAIN-STOP
- Status last verified
- Jan 2020
- First submitted
- 28 Oct 2016
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32104059
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02950233
- Acronym / sponsor ID
- PAIN-STOP / 2016-001-PS
- Conditions
- Pain, Postoperative
- Keywords
- postoperative pain, VATS, activities of daily living, quality of life
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment was slower than expected and study drug reached expiry
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Population Health Research InstituteUniversity, hospital or other
- Study start
- 4 May 2017 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Mar 2019 (actual)
- First posted
- 1 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| NMDA active + Steroid placebo | Experimental | Drug: NMDA active, Drug: Steroid placeboNMDA 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. |
| Steroid active + NMDA placebo | Experimental | Drug: Steroid active, Drug: NMDA placeboNMDA 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. |
| NMDA active + Steroid active | Experimental | Drug: NMDA active, Drug: Steroid activeNMDA 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. |
| NMDA placebo + Steroid placebo | Placebo comparator | Drug: NMDA placebo, Drug: Steroid placeboNMDA 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 18-75 years of age,
- Planned elective VATS pulmonary lobectomy,
- Provide written informed consent to participate.
Key exclusion criteria (10 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NMDA activeNMDA 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]). | Drug | NMDA active + Steroid active, NMDA active + Steroid placebo |
| Steroid activeSteroid 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. | Drug | NMDA active + Steroid active, Steroid active + NMDA placebo |
| NMDA placeboNMDA 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]). | Drug | NMDA placebo + Steroid placebo, Steroid active + NMDA placebo |
| Steroid placeboSteroid 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. | Drug | NMDA active + Steroid placebo, NMDA placebo + Steroid placebo |
Primary outcome
Recruitment
Time frame: 6 months
Ability to recruit 90% of eligible patients.
Recruitment
Time frame: 6 months
Ability to recruit at least 4 patients per month per site, and complete the recruitment over a 6-month period.
Follow-up
Time frame: 9 months
Ability to obtain follow-up in >90% of enrolled patients, at three months.
9 secondary outcomes
NRS - Incidence of PPSP
Time frame: 3 months
NRS - Incidence of PPSP with movement evoked
Time frame: 3 months
Rate of change of postoperative pain intensity
Time frame: 3 months
Use of narcotic analgesic medication
Time frame: 3 months
Presence of NP
Time frame: 3 months
BPI score
Time frame: 3 months
Thoracic surgery specific activity limitations
Time frame: 3 months
Change in global health status
Time frame: 3 months
Difference in Quality of Life
Time frame: 3 months
Results and safety
The study was stopped early (reason given: Recruitment was slower than expected and study drug reached expiry). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Derived from this study: PubMed 32104059Shanthanna 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
PJ Devereaux, MD, PhD study chair
McMaster University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NMDA active and Steroid active in people with Pain, Postoperative, run by Population Health Research Institute at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment was slower than expected and study drug reached expiry). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02950233, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.