Acute PainPhase 4NCT02489630
Low Dose Ketamine as an Adjunct to Opiates for Acute Pain in the Emergency Department
A Phase 4 study testing Ketamine, Normal Saline and opiate analgesic in people with Acute Pain and Pain, run by Carilion Clinic.
Trial summary
This study investigates the use of low doses of ketamine, along with opiate pain medication, is more effective at controlling the acute pain of patients in the emergency department than opiate pain medication alone. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Pain, Pain
- What is being tested?
- Ketamine, Normal Saline and opiate analgesic
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 116 participants
- Where
- No sites listed yet
- Study dates
- Sep 2013to Mar 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Greater than 18 years but less than 70 years old.
- Exhibiting pain defined on a numerical rating scale (NRS-11 [Farrar et al. 2001]) score of equal to or greater than 6 out of 10
- Deemed by the treating EM physician to require opioid analgesia.
Who cannot join
- Respiratory, hemodynamic or neurologic compromise, as determined by observation of signs of respiratory distress, systolic blood pressure less than 90 mmHg or systolic/diastolic blood pressure greater than 160/90, or a Glasgow -Coma Score less than 15.
- A history of chronic ventilation, dialysis or with previously diagnosed cirrhosis or hepatitis by istory.
- Active psychosis.
- Clinical intoxication.
- Known sensitivity to any study drug.
- An inability to understand the NRS-11 pain measurement scale.
Show all 12Show fewer
- Presentation with headache or chest pain.
- Pregnancy.
- A lack of decision-making capacity.
- A pain score less than 6 on the NRS-11 scale.
- A concern by the treating physician or study personnel of current or prior history of narcotic abuse, or other secondary gain.
- Previously participated in the study.
About this study
This study investigates the use of low doses of ketamine, along with opiate pain medication, is more effective at controlling the acute pain of patients in the emergency department than opiate pain medication alone. In addition, this study examines whether patients treated with low doses of ketamine, along with opiate pain medication, will require less opiate pain medication to control their pain, and whether these patients are equally happy with their pain control as patients who receive only opiate pain medication.
Read the detailed description
This randomized, double blinded, placebo controlled study investigates the use of low-dose ketamine, in conjunction to standard opiate treatment, as compared to placebo plus standard opiate treatment, for acute painful conditions in the ED setting. The investigators hypothesize that patients treated with ketamine will require less opiate for similar levels of pain relief up to 2 hours from initiation of treatment, with similar levels of patient satisfaction and an acceptable side effect profile.
Once seen by a physician, potential patients will receive provider-determined opiate treatment for their painful condition, prior to the informed consent process to ensure that treatment is not delayed. Once identified for inclusion, patients will receive informed consent and, upon consent, will subsequently be randomized through block randomization into one of two study groups. Each study group will contain at least 50 subjects. Randomization will be determined using a table of random numbers, using a restricted randomization scheme to ensure roughly equal numbers in each group. Group assignments will be sealed in opaque envelopes to be opened sequentially by the investigators. Group assignments will not indicate whether it is the treatment or the control group. At this time (T0), an initial NRS-11 score will be obtained. The NRS-11 is an 11-point scale on which patients rate their level of pain from 0 ("no pain") to 10 ("worst pain imaginable"). If, after initial analgesic, pain level is <6, patients will be asked again in 15 min. If at this time it is still <6, they will not proceed in the study. The intervention group will receive 0.1 mg/kg of ketamine given over 1 minute, and the control group will receive an equivalent volume of normal saline; both groups will have received a provider-determined dose of opiate analgesia prior to enrollment. At thirty-minute intervals, subjects will be asked their level of pain, if they need more pain control and will be evaluated for the presence of side effects (hallucinations, dysphoria, weakness, diplopia, nausea, vomiting, dizziness, itching and bradypnea) as well as sedation as defined by Ramsay score of greater than 2. Repeat doses of pain medication will be given as 0.05 mg/kg morphine or equivalent dose of opioid analgesic. Total opiate dosage and number of repeat doses given at the end of 120 minutes will be recorded. At each time interval, as well as at the end of 120 minutes (T120), patient satisfaction with pain control will be recoded on the 4-point Likert scale, with 0 being "completely unsatisfied" and 3 being "very satisfied".
- Conditions
- Acute Pain, Pain
- Being tested
- Ketamine, Normal Saline, opiate analgesic
- Medical subject headings
- Acute Pain, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar
0.1mg/kg ketamine IV
Normal SalineDrug
Also called NS, saline
1ml/kg normal saline placebo
opiate analgesicDrug
0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | 0.1 mg/kg ketamine + opiate analgesic Receives: Drug: Ketamine; Drug: opiate analgesic |
| Placebo | Placebo comparator | 0.1 mL/kg normal saline + opiate analgesic Receives: Drug: Normal Saline; Drug: opiate analgesic |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Level of Pain Control as Reported on the NRS-11
Patient-reported pain scores on numerical rating scale (NRS) -11 pain scale (where 0 indicates no pain at all, 10 indicates the most severe pain). "Initial" group were patients enrolled and randomized in to the study, assessments were taken at the time of enrollment/randomization in to the study (up to 20 min prior to T=0). T = 0 min assessments were conducted at the time of medication administration (study allowed for an up to 20-minute delay in receiving study drug in order to retrieve study drug from secure storage, nursing documentation and patient verification prior to administration).
Measured: 20 min pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale
Patient-reported score regarding satisfaction with pain control, reported on a 4-point Likert scale (1-4, where 1 is the lowest satisfaction score possible and 4 is the highest satisfaction score possible). No data is reported for T = 0 min, as that assessment was conducted concurrently with initial medication dosing (since patients were at that point receiving their first pain control efforts, they could not yet assess their satisfaction with those efforts).
Measured: 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Secondary outcomes (1)
Difference in Opiate Dosage Between Study Arms in Morphine Equivalents
Average difference in opiate dosage between study arms, calculated in morphine equivalents. "Initial" indicates at first dose of opioid administration, up to 20 mins prior to study drug administration, and from 0 min to 120 min after study drug administration.
Measured: 20 mins pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2015 (estimated)
- Study startSep 2013
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Acute PainStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carilion Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Virginia Polytechnic Institute and State University, University of Memphis
- Responsible party
- Sponsor
- Investigators
- Corey R Heitz, MD, Principal investigator, Physician
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02489630
- Sponsor's protocol ID
- 08302015
- Status last verified
- Feb 2021
- First submitted
- 30 Jun 2015
- Last updated
- 12 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ahern TL, Herring AA, Stone MB, Frazee BW. Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain. Am J Emerg Med. 2013 May;31(5):847-51. doi: 10.1016/j.ajem.2013.02.008. Epub 2013 Apr 18.
PubMed 23602757Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med. 2014 Nov;21(11):1193-202. doi: 10.1111/acem.12510.
PubMed 25377395Galinski M, Dolveck F, Combes X, Limoges V, Smail N, Pommier V, Templier F, Catineau J, Lapostolle F, Adnet F. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med. 2007 May;25(4):385-90. doi: 10.1016/j.ajem.2006.11.016.
PubMed 17499654Jennings PA, Cameron P, Bernard S, Walker T, Jolley D, Fitzgerald M, Masci K. Morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: a randomized controlled trial. Ann Emerg Med. 2012 Jun;59(6):497-503. doi: 10.1016/j.annemergmed.2011.11.012. Epub 2012 Jan 13.
PubMed 22243959Johansson P, Kongstad P, Johansson A. The effect of combined treatment with morphine sulphate and low-dose ketamine in a prehospital setting. Scand J Trauma Resusc Emerg Med. 2009 Nov 27;17:61. doi: 10.1186/1757-7241-17-61.
PubMed 19943920Kissin I, Bright CA, Bradley EL Jr. The effect of ketamine on opioid-induced acute tolerance: can it explain reduction of opioid consumption with ketamine-opioid analgesic combinations? Anesth Analg. 2000 Dec;91(6):1483-8. doi: 10.1097/00000539-200012000-00035.
PubMed 11094005
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Dose Ketamine as an Adjunct to Opiates for Acute Pain in the Emergency Department
- ClinicalTrials.gov ID
- NCT02489630
- Acronym / sponsor ID
- 08302015
- Conditions
- Acute Pain, Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Carilion ClinicUniversity, hospital or other
- Collaborators
- Virginia Polytechnic Institute and State University, University of Memphis
- Study start
- Sep 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 3 Jul 2015 (estimated)
- Results
- Posted 12 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study investigates the use of low doses of ketamine, along with opiate pain medication, is more effective at controlling the acute pain of patients in the emergency department than opiate pain medication alone. In addition, this study examines whether patients treated with low doses of ketamine, along with opiate pain medication, will require less opiate pain medication to control their pain, and whether these patients are equally happy with their pain control as patients who receive only opiate pain medication.
Detailed description
This randomized, double blinded, placebo controlled study investigates the use of low-dose ketamine, in conjunction to standard opiate treatment, as compared to placebo plus standard opiate treatment, for acute painful conditions in the ED setting. The investigators hypothesize that patients treated with ketamine will require less opiate for similar levels of pain relief up to 2 hours from initiation of treatment, with similar levels of patient satisfaction and an acceptable side effect profile.
Once seen by a physician, potential patients will receive provider-determined opiate treatment for their painful condition, prior to the informed consent process to ensure that treatment is not delayed. Once identified for inclusion, patients will receive informed consent and, upon consent, will subsequently be randomized through block randomization into one of two study groups. Each study group will contain at least 50 subjects. Randomization will be determined using a table of random numbers, using a restricted randomization scheme to ensure roughly equal numbers in each group. Group assignments will be sealed in opaque envelopes to be opened sequentially by the investigators. Group assignments will not indicate whether it is the treatment or the control group. At this time (T0), an initial NRS-11 score will be obtained. The NRS-11 is an 11-point scale on which patients rate their level of pain from 0 ("no pain") to 10 ("worst pain imaginable"). If, after initial analgesic, pain level is <6, patients will be asked again in 15 min. If at this time it is still <6, they will not proceed in the study. The intervention group will receive 0.1 mg/kg of ketamine given over 1 minute, and the control group will receive an equivalent volume of normal saline; both groups will have received a provider-determined dose of opiate analgesia prior to enrollment. At thirty-minute intervals, subjects will be asked their level of pain, if they need more pain control and will be evaluated for the presence of side effects (hallucinations, dysphoria, weakness, diplopia, nausea, vomiting, dizziness, itching and bradypnea) as well as sedation as defined by Ramsay score of greater than 2. Repeat doses of pain medication will be given as 0.05 mg/kg morphine or equivalent dose of opioid analgesic. Total opiate dosage and number of repeat doses given at the end of 120 minutes will be recorded. At each time interval, as well as at the end of 120 minutes (T120), patient satisfaction with pain control will be recoded on the 4-point Likert scale, with 0 being "completely unsatisfied" and 3 being "very satisfied".
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: Ketamine, Drug: opiate analgesic0.1 mg/kg ketamine + opiate analgesic |
| Placebo | Placebo comparator | Drug: Normal Saline, Drug: opiate analgesic0.1 mL/kg normal saline + opiate analgesic |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Greater than 18 years but less than 70 years old.
- Exhibiting pain defined on a numerical rating scale (NRS-11 [Farrar et al. 2001]) score of equal to or greater than 6 out of 10
- Deemed by the treating EM physician to require opioid analgesia.
Key exclusion criteria (12 listed)
- Respiratory, hemodynamic or neurologic compromise, as determined by observation of signs of respiratory distress, systolic blood pressure less than 90 mmHg or systolic/diastolic blood pressure greater than 160/90, or a Glasgow -Coma Score less than 15.
- A history of chronic ventilation, dialysis or with previously diagnosed cirrhosis or hepatitis by istory.
- Active psychosis.
- Clinical intoxication.
- Known sensitivity to any study drug.
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 |
|---|---|---|
| KetamineAlso: Ketalar0.1mg/kg ketamine IV | Drug | Ketamine |
| Normal SalineAlso: NS, saline1ml/kg normal saline placebo | Drug | Placebo |
| opiate analgesic0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request | Drug | Ketamine, Placebo |
Primary outcome
Change in Level of Pain Control as Reported on the NRS-11
Time frame: 20 min pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Patient-reported pain scores on numerical rating scale (NRS) -11 pain scale (where 0 indicates no pain at all, 10 indicates the most severe pain). "Initial" group were patients enrolled and randomized in to the study, assessments were taken at the time of enrollment/randomization in to the study (up to 20 min prior to T=0). T = 0 min assessments were conducted at the time of medication administration (study allowed for an up to 20-minute delay in receiving study drug in order to retrieve study drug from secure storage, nursing documentation and patient verification prior to administration).
Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale
Time frame: 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Patient-reported score regarding satisfaction with pain control, reported on a 4-point Likert scale (1-4, where 1 is the lowest satisfaction score possible and 4 is the highest satisfaction score possible). No data is reported for T = 0 min, as that assessment was conducted concurrently with initial medication dosing (since patients were at that point receiving their first pain control efforts, they could not yet assess their satisfaction with those efforts).
1 secondary outcome
Difference in Opiate Dosage Between Study Arms in Morphine Equivalents
Time frame: 20 mins pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23602757Ahern TL, Herring AA, Stone MB, Frazee BW. Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain. Am J Emerg Med. 2013 May;31(5):847-51. doi: 10.1016/j.ajem.2013.02.008. Epub 2013 Apr 18.
- Background: PubMed 25377395Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med. 2014 Nov;21(11):1193-202. doi: 10.1111/acem.12510.
- Background: PubMed 17499654Galinski M, Dolveck F, Combes X, Limoges V, Smail N, Pommier V, Templier F, Catineau J, Lapostolle F, Adnet F. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med. 2007 May;25(4):385-90. doi: 10.1016/j.ajem.2006.11.016.
- Background: PubMed 22243959Jennings PA, Cameron P, Bernard S, Walker T, Jolley D, Fitzgerald M, Masci K. Morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: a randomized controlled trial. Ann Emerg Med. 2012 Jun;59(6):497-503. doi: 10.1016/j.annemergmed.2011.11.012. Epub 2012 Jan 13.
- Background: PubMed 19943920Johansson P, Kongstad P, Johansson A. The effect of combined treatment with morphine sulphate and low-dose ketamine in a prehospital setting. Scand J Trauma Resusc Emerg Med. 2009 Nov 27;17:61. doi: 10.1186/1757-7241-17-61.
- Background: PubMed 11094005Kissin I, Bright CA, Bradley EL Jr. The effect of ketamine on opioid-induced acute tolerance: can it explain reduction of opioid consumption with ketamine-opioid analgesic combinations? Anesth Analg. 2000 Dec;91(6):1483-8. doi: 10.1097/00000539-200012000-00035.
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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.
Corey R Heitz, MD principal investigator
Physician
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine, Normal Saline and opiate analgesic in people with Acute Pain and Pain, run by Carilion Clinic.
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 12 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: finished, as of the sponsor's last update on 12 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Level of Pain Control as Reported on the NRS-11 (time frame: 20 min pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration). The study lists 2 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 NCT02489630, which also lists 6 linked publications.
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 12 Mar 2021.