Ignite Creation Date:
2024-05-06 @ 11:05 AM
Last Modification Date:
2024-10-26 @ 12:39 PM
Study NCT ID:
NCT03426137
Status:
TERMINATED
Last Update Posted:
2021-04-27
First Post:
2018-01-16
Brief Title:
Relieving Acute Pain RAP Study A Pilot Study
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
Relieving Acute Pain RAP A Pilot Study
Status:
TERMINATED
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The focus of the project has shifted to publishing a protocol for future trials because we were unable to recruit Three participants signed the consent forms but withdrew before the randomization
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The United States US faces a crisis of pain management According to the 2012 National Health Interview Survey almost 50 million adults in the US reported having significant chronic or severe pain Nahin 2015 Doctors in the US still prescribe opioids across the board for pain despite a growing recognition of an epidemic of opioid overdose and use disorder Few solutions have been successfully proposed and implemented Placebos represent a novel and potentially fruitful means of addressing this issue However clinicians often use placebos deceptively and with little rationale or evidence of benefit making their use ethically problematic In contrast with their typical current use a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects Recently we reviewed a database of placebo studies including 22 studies in both animals and humans hinting of evidence that placebos may work as a dose extender of active painkillers Placebos given after repeated administration of active treatments can acquire medication-like effects based on learning mechanisms
Here we will test if dose-extending placebos are effective in relieving clinical acute pain in opioid patients with traumatic pain Patients will be randomized to three arms Arm 1 will be a Full Dose FD group which will receive all NSAIDs as described in the Guidelines for NSAID use in Orthopedic Patients and Oxycodone 5mg Arm 2 will be a Partial Reinforcement PR group which will receive NSAIDs Oxycodone 5mg and placebos to reach a 50 reduction of the total intake of opioids Finally Arm 3 will be a Control C group receiving NSAIDs and placebos Patients will be assigned to one of three arms according to a 111 schedule of randomization Study IDs will be generated by the pharmacy and blinding will occur by ensuring that oxycodone and placebos look smell and taste identical Rescue therapy will be provided as needed This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments the typical regimens of painkiller applications and the ways in which treatments are evaluated
Here we will test if dose-extending placebos are effective in relieving clinical acute pain in opioid patients with traumatic pain Patients will be randomized to three arms Arm 1 will be a Full Dose FD group which will receive all NSAIDs as described in the Guidelines for NSAID use in Orthopedic Patients and Oxycodone 5mg Arm 2 will be a Partial Reinforcement PR group which will receive NSAIDs Oxycodone 5mg and placebos to reach a 50 reduction of the total intake of opioids Finally Arm 3 will be a Control C group receiving NSAIDs and placebos Patients will be assigned to one of three arms according to a 111 schedule of randomization Study IDs will be generated by the pharmacy and blinding will occur by ensuring that oxycodone and placebos look smell and taste identical Rescue therapy will be provided as needed This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments the typical regimens of painkiller applications and the ways in which treatments are evaluated
Detailed Description:
Overview
We will screen 500 patients from the Shock Trauma Center to recruit a total of 159 53 per arm to participate in a pilot study aimed at reducing use of opioids Participants will meet all of the eligibility criteria and none of the exclusion criteria After enrollment participants will be blindly allocated to one of three randomization arms by means of de-identified Study IDs corresponding to treatment arms Study IDs will be generated by the pharmacy and blinding will be ensured by creating study drugs that look smell and taste identical The pharmacy will create and dispense identical study drugs in terms of appearance smell and taste Only the blinding coordinator will know the identity of patients in each treatment arm Arm 1 will be a Full Dose FD group which will receive Non-Steroidal Anti-Inflammatory Drugs NSAIDs dosed in accordance with the University of Maryland Shock Trauma Center STC Guidelines for NSAIDs and Oxycodone 5mg Arm 2 will be a Partial Reinforcement PR group which will receive NSAIDs Oxycodone 5mg and placebos to reach a 50 reduction of the total intake of opioids Finally Arm 3 will be a Control C group receiving NSAIDs and placebos Patients will be assigned to one of these three arms according to a 111 schedule of randomization The patient will start receiving study medication as part of his or her pain management as soon as possible after admission to the hospital and enrollment in the study ideally as their first dose of pain-management medication Rescue therapy will be provided as needed
All enrolled patients will receive an Adult Pain Management Service APMS consult APMS will work with the study and clinical teams to ensure that all treatment protocols are met and be available to address any issues that may arise The APMS provider will work with the primary service to determine the most effective NSAID as described in their guidelines
Other than the study medication Oxycodone and placebo all participants will be treated in accordance with the current standard of care at the University of Maryland Shock Trauma Center This includes intravenous Toradol every 8 hours for 24 hours followed by oral NSAIDs round the clock until pain is minimal The timing of administration will be the same for participants in all three arms - they will receive their arms treatment Oxycodone Oxycodone alternating with placebo or no additional medication beyond standard of care NSAIDs round the clock for the first 24 hours followed by every hours for the remainder of hospitalization All patients will receive intravenous Dilaudid every hour for rescue or break through pain In addition all patients will be discharged on Oxycodone tablets 5mg every 3 hours as needed
In Arm 2 the first four doses of study drug will be Oxycodone 5mg to condition them to its effects Afterwards they will receive alternating Oxycodone 5mg and placebo according to one of four repeating sequences During data analysis we will test whether the sequence of administration has an effect on outcomes Participants in Arm 2 will never receive more than 2 doses of placebo in a row This administration schedule will be repeated for the remainder of hospitalization
Prior to patients enrollment
The intent of this study is to enroll 159 patients with trauma into this study to compare strategies to reduce opioid use during the management of acute pain Patients will be screened on admission to the Shock Trauma Center Eligible patients will meet all of the inclusion criteria and none of the exclusion criteria Patients with trauma will be considered for enrollment and be flagged for screening A plan by the primary service to adhere to The Shock Trauma Protocol for NSAID use is also a requirement for enrollment Eligible participants will be informed and have the opportunity to discuss the nature of the study potential for treatment allocation and riskbenefits For those who agree to participate the approved Informed Consent Form and HIPAA authorization form will be signed The research staff will explain to the participant what tasks they are expected to complete during this study answer any questions they may have and ensure comprehension by completing the Informed Consent Checklist which asks participants to verbally report their understanding of the study purpose and procedures among other key points
Allocation to treatment group
After the participant discusses and signs the consent form a staff member will call the pharmacy to inform them of the participants de-identified Screening number The pharmacy will then randomly assign that participant a Study ID corresponding randomly to one of the three treatment groups and handle drug logistics sourcing processing and administration for the remainder of Phase I The patient will start receiving the study drug within 24 hours of being able to take narcotics ideally as hisher first narcotic medication All staff involved with the protocol will be fully trained on it and will be given study team member emergency contacts in case of incident
Blinding
Oxycodone and Placebo will be identical in terms of appearance taste and smell so as to keep both the investigators and participants blind to their treatment allocation Oxycodone and placebo oral suspensions will be manufactured by the IDS Oxycodone solution will be made from tablets to ensure blinding In this way both Oxycodone and placebo will look identical for taste color and smell This will help not only to blind the study but also facilitate study drug administration given that patients may be intubated All research personnel aside from the pharmacists and team members responsible for final review and write-up of the study will be blinded to participants treatment groups The pharmacy will dispense medications for each participant that will correspond with their allocated treatment group For participants in the Partial Reduction group Arm 2 the pharmacy will dispense the study drug In summary participants in Arm 2 will receive four doses of Oxycodone 5mg followed by one of four repeating schedules of administration alternating between Oxycodone 5mg and placebo
Hospitalization window Enrollment - End of Hospitalization
Pain ratings will be recorded as usual within 20 to 90 minutes after each study drug administration Also participants will be given the option to complete a set of psychological questionnaires during the time in the hospital or by the time of their first follow-up visit Questionnaires unrelated to pain will be optional Although we cannot change the wording of our validated pain questionnaires staff will be trained to use the phrasing such as how well they are able to perform their daily activities how well they are able to interact with visitorsfamily and how well they are sleeping whenever possible and that surveys andquestions during the follow-up phase will also take this non-pain-centric approach
Discharge
Participants will be monitored for subsequent use of opioids at the first post-discharge visit at approximately 2 weeks and within month 1 3 and 6 for follow-ups The research team via calls letters emails or texts REDCap Qualtrics MetricWire will be used to facilitate the communication via text and emails The team member will ask the participant questions about their health and medication use In addition a phone application may be developed or the data collection system Qualtrics used to gather information about participants medication use and health during the follow-up period Although the wording of the validated Pain Questionnaires we will use during hospitalization cannot be changed during the follow-up phase we will aim to frame questions about pain intensity and interference with function in such a way as to avoid nocebo effects ie asking how well they are able to perform their daily activities how well they are able to interact with visitorsfamily and how well they are sleeping instead of how much pain are they experiencing
Duration of the clinical trial
Hospitalization window starting as soon after admission as possible for a projected minimum of 2 days with follow-up at approximately 2 weeks coinciding with their first post-discharge visit with their clinician and months 1 3 and 6
Rescue plan
All patients will have the same rescue medicine available for break through pain intravenous Dilaudid every hour
Participants in each of the three randomization arms will have access to opioid rescue medication Dilaudid as needed via a standing order for breakthrough pain rated as Severe The rate of use pf rescue therapy will be evaluated as a primary endpoints Participants who request more than 3 doses of rescue medication in a row will be withdrawn from the study and referred to APMS for further pain management
Primary and secondary outcomes To be measured daily during hospitalization
1 Acute clinical and functional pain acute pain improvement opioid intake rate of request of rescue therapies
Primary and secondary outcomes To be measured daily during the follow-up
1 Use frequency and intensity of opioid prescriptions
2 Development of dependence andor addiction problems
We will screen 500 patients from the Shock Trauma Center to recruit a total of 159 53 per arm to participate in a pilot study aimed at reducing use of opioids Participants will meet all of the eligibility criteria and none of the exclusion criteria After enrollment participants will be blindly allocated to one of three randomization arms by means of de-identified Study IDs corresponding to treatment arms Study IDs will be generated by the pharmacy and blinding will be ensured by creating study drugs that look smell and taste identical The pharmacy will create and dispense identical study drugs in terms of appearance smell and taste Only the blinding coordinator will know the identity of patients in each treatment arm Arm 1 will be a Full Dose FD group which will receive Non-Steroidal Anti-Inflammatory Drugs NSAIDs dosed in accordance with the University of Maryland Shock Trauma Center STC Guidelines for NSAIDs and Oxycodone 5mg Arm 2 will be a Partial Reinforcement PR group which will receive NSAIDs Oxycodone 5mg and placebos to reach a 50 reduction of the total intake of opioids Finally Arm 3 will be a Control C group receiving NSAIDs and placebos Patients will be assigned to one of these three arms according to a 111 schedule of randomization The patient will start receiving study medication as part of his or her pain management as soon as possible after admission to the hospital and enrollment in the study ideally as their first dose of pain-management medication Rescue therapy will be provided as needed
All enrolled patients will receive an Adult Pain Management Service APMS consult APMS will work with the study and clinical teams to ensure that all treatment protocols are met and be available to address any issues that may arise The APMS provider will work with the primary service to determine the most effective NSAID as described in their guidelines
Other than the study medication Oxycodone and placebo all participants will be treated in accordance with the current standard of care at the University of Maryland Shock Trauma Center This includes intravenous Toradol every 8 hours for 24 hours followed by oral NSAIDs round the clock until pain is minimal The timing of administration will be the same for participants in all three arms - they will receive their arms treatment Oxycodone Oxycodone alternating with placebo or no additional medication beyond standard of care NSAIDs round the clock for the first 24 hours followed by every hours for the remainder of hospitalization All patients will receive intravenous Dilaudid every hour for rescue or break through pain In addition all patients will be discharged on Oxycodone tablets 5mg every 3 hours as needed
In Arm 2 the first four doses of study drug will be Oxycodone 5mg to condition them to its effects Afterwards they will receive alternating Oxycodone 5mg and placebo according to one of four repeating sequences During data analysis we will test whether the sequence of administration has an effect on outcomes Participants in Arm 2 will never receive more than 2 doses of placebo in a row This administration schedule will be repeated for the remainder of hospitalization
Prior to patients enrollment
The intent of this study is to enroll 159 patients with trauma into this study to compare strategies to reduce opioid use during the management of acute pain Patients will be screened on admission to the Shock Trauma Center Eligible patients will meet all of the inclusion criteria and none of the exclusion criteria Patients with trauma will be considered for enrollment and be flagged for screening A plan by the primary service to adhere to The Shock Trauma Protocol for NSAID use is also a requirement for enrollment Eligible participants will be informed and have the opportunity to discuss the nature of the study potential for treatment allocation and riskbenefits For those who agree to participate the approved Informed Consent Form and HIPAA authorization form will be signed The research staff will explain to the participant what tasks they are expected to complete during this study answer any questions they may have and ensure comprehension by completing the Informed Consent Checklist which asks participants to verbally report their understanding of the study purpose and procedures among other key points
Allocation to treatment group
After the participant discusses and signs the consent form a staff member will call the pharmacy to inform them of the participants de-identified Screening number The pharmacy will then randomly assign that participant a Study ID corresponding randomly to one of the three treatment groups and handle drug logistics sourcing processing and administration for the remainder of Phase I The patient will start receiving the study drug within 24 hours of being able to take narcotics ideally as hisher first narcotic medication All staff involved with the protocol will be fully trained on it and will be given study team member emergency contacts in case of incident
Blinding
Oxycodone and Placebo will be identical in terms of appearance taste and smell so as to keep both the investigators and participants blind to their treatment allocation Oxycodone and placebo oral suspensions will be manufactured by the IDS Oxycodone solution will be made from tablets to ensure blinding In this way both Oxycodone and placebo will look identical for taste color and smell This will help not only to blind the study but also facilitate study drug administration given that patients may be intubated All research personnel aside from the pharmacists and team members responsible for final review and write-up of the study will be blinded to participants treatment groups The pharmacy will dispense medications for each participant that will correspond with their allocated treatment group For participants in the Partial Reduction group Arm 2 the pharmacy will dispense the study drug In summary participants in Arm 2 will receive four doses of Oxycodone 5mg followed by one of four repeating schedules of administration alternating between Oxycodone 5mg and placebo
Hospitalization window Enrollment - End of Hospitalization
Pain ratings will be recorded as usual within 20 to 90 minutes after each study drug administration Also participants will be given the option to complete a set of psychological questionnaires during the time in the hospital or by the time of their first follow-up visit Questionnaires unrelated to pain will be optional Although we cannot change the wording of our validated pain questionnaires staff will be trained to use the phrasing such as how well they are able to perform their daily activities how well they are able to interact with visitorsfamily and how well they are sleeping whenever possible and that surveys andquestions during the follow-up phase will also take this non-pain-centric approach
Discharge
Participants will be monitored for subsequent use of opioids at the first post-discharge visit at approximately 2 weeks and within month 1 3 and 6 for follow-ups The research team via calls letters emails or texts REDCap Qualtrics MetricWire will be used to facilitate the communication via text and emails The team member will ask the participant questions about their health and medication use In addition a phone application may be developed or the data collection system Qualtrics used to gather information about participants medication use and health during the follow-up period Although the wording of the validated Pain Questionnaires we will use during hospitalization cannot be changed during the follow-up phase we will aim to frame questions about pain intensity and interference with function in such a way as to avoid nocebo effects ie asking how well they are able to perform their daily activities how well they are able to interact with visitorsfamily and how well they are sleeping instead of how much pain are they experiencing
Duration of the clinical trial
Hospitalization window starting as soon after admission as possible for a projected minimum of 2 days with follow-up at approximately 2 weeks coinciding with their first post-discharge visit with their clinician and months 1 3 and 6
Rescue plan
All patients will have the same rescue medicine available for break through pain intravenous Dilaudid every hour
Participants in each of the three randomization arms will have access to opioid rescue medication Dilaudid as needed via a standing order for breakthrough pain rated as Severe The rate of use pf rescue therapy will be evaluated as a primary endpoints Participants who request more than 3 doses of rescue medication in a row will be withdrawn from the study and referred to APMS for further pain management
Primary and secondary outcomes To be measured daily during hospitalization
1 Acute clinical and functional pain acute pain improvement opioid intake rate of request of rescue therapies
Primary and secondary outcomes To be measured daily during the follow-up
1 Use frequency and intensity of opioid prescriptions
2 Development of dependence andor addiction problems
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None