PainPhase 4NCT02642718
Pre-operative Ketorolac Administration Has no Pre-emptive Analgesic Effect Following Total Abdominal Hysterectomy
A Phase 4 study testing Ketorolac Tromethamine in people with Pain, run by Hospital Arquitecto Marcide at 2 sites in 2 countries.
Trial summary
Background: Experimental models using short duration noxious stimuli have led to the concept of pre-emptive analgesia. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), has been shown to have a post-operative narcotic sparing effect when given pre-operatively and alternatively to not have this effect. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Pain
- What is being tested?
- Ketorolac Tromethamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Apr 2001to Nov 2001
- Phase
- Phase 4
- 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 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- normal height and weight
- ASA class I, II, III
- elective surgery
- surgery time between 30-150 min
- understanding of the Visual Analog Scale (VAS)
- no allergies or intolerance to NSAIDs or anesthetics
- no psychiatric illness.
Who cannot join
- renal deterioration
- history of peptic ulceration
- asthma
- coagulopathy
- cognitive impairment
- inability to use the Patient Controlled Analgesia (PCA) device
Show all 11Show fewer
- history of chronic pain syndromes
- history of chronic use of analgesics, sedatives, opioids or steroids
- liver or hematologic disease
- a history of drug or alcohol abuse
- therapy with NSAIDs, anticoagulants, or lithium.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Spain1 site
Complexo Hospitalario Arquitecto Marcide-Prof. Novoa Santos
Ferrol, A Coruña, 15405
United Kingdom1 site
Oxford University Hospitals NHS Trust
Oxford, Oxfordshire, OX3 9DU
About this study
Background: Experimental models using short duration noxious stimuli have led to the concept of pre-emptive analgesia. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), has been shown to have a post-operative narcotic sparing effect when given pre-operatively and alternatively to not have this effect. This study was undertaken to determine whether a single intravenous dose of ketorolac would result in decreased post-operative pain and narcotic requirements.
Methods: In a double-blind, randomized controlled trial, 48 women undergoing abdominal hysterectomy were studied. Patients in the ketorolac group received 30 mg of intravenous ketorolac 30 minutes before surgical incision, while the control group received normal saline. The post-operative analgesia was performed with a continuous infusion of tramadol at 12 mg/hour with the possibility of a 10 mg bolus every 10 minutes. Pain was assessed using the Visual Analog Scale (VAS), tramadol consumption and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16 and 24 hours post-operatively. We quantified times to rescue analgesic (morphine), adverse effects and patient satisfaction.
Read the detailed description
Damage to tissues has been shown to provoke a magnified reaction to noxious stimuli, peripherally by diminishing the threshold of nociceptive afferent nerve terminals and centrally by augmenting the excitability of second-order sensory neurons in the spinal cord; later resulting in an amplification and extension of postoperative pain after surgery. Hence, much research has focused on procedures to avoid these central neuroplastic changes through the usage of preemptive analgesia.
Experimental models have conducted to the idea of 'preemptive analgesia' . The decrement of afferent nociceptive inputs to the spinal cord using analgesic techniques started before the initial painful stimulus avoids or attenuates the formation of spinal hyperexcitabilty and avoids the transformed processing of afferent input, leading to less postoperative pain. Whether such experimental models are applicable to the noxious circumstances occurring during surgery is controversial.
Although preemptive analgesia with different agents have been successful in experimental animals, conclusions from human studies remain in conflict. A diversity of agents have been analyzed for their conceivable preemptive analgesic effects: local anesthetics, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, opioids, magnesium, cytokine synthesis inhibitors, ketamine, and tricyclic antidepressants.
Scientific research enabling an understanding of the molecular mechanisms of nociception has disclosed a considerable function of cytokines and prostaglandins (PG). Hyperexcitability also appears peripherally in nerve endings at the location of surgical tissue damage and is mediated in part by prostaglandins. Evidence is accumulating that products of the cyclooxygenase pathway may be engaged in the elaboration of central sensitization. Drugs that block the formation of prostaglandins such as NSAIDs might therefore be assumed to avoid or minimize the formation of this peripheral and central hyperexcitability. Their central analgesic actions are effected by averting spinal prostaglandin synthesis and attenuating liberation of neurotransmitters from the primary afferent terminals and spinal interneurons.
Sporadic studies have established some considerable preemptive benefit of NSAIDs. As a result, the objective of this study was to ascertain the impact of a NSAID, ketorolac, on pain severity and analgesic requirement, in the early postoperative period.
Ketorolac is a nonselective NSAID that blocks cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) enzymes and as a result blocks the formation of prostaglandins attenuating the sensitization procedures. The antinociceptive and anti-inflammatory action of NSAIDs may be associated to the suppression of nitric oxide synthase activation, decreased generation of proinflammatory cytokines, and lipoxine activation. Consequently, this multidirectional activity indicates that there may be the probability of adjusting the nociception process by the employment of these drugs perioperatively.
To our knowledge, no prior controlled study has determined the effectiveness of preoperative intravenous ketorolac compared to placebo in patients who underwent abdominal hysterectomies. Thus, this clinical trial was conceived to explore the postoperative analgesic efficiency and opioid-sparing action of a single dose of intravenous ketorolac in contrast with placebo administered preoperatively.
- Conditions
- Pain
- Being tested
- Ketorolac Tromethamine, Placebo
- Keywords
- preemptive analgesia, postoperative pain, NSAIDs, ketorolac, abdominal hysterectomy
- Medical subject headings
- Pain, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketorolac TromethamineDrug
Also called ketorolac
In the operating room, the anesthesiologist administered ketorolac (30 mg) in 50 mL of 0.9 % saline intravenously to patients in the ketorolac group 30 minutes before surgical incision (a single dose).
PlaceboOther
In the operating room, the anesthesiologist administered 50 mL of 0.9 % saline intravenously to patients in the control group 30 minutes before surgical incision
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | In the operating room, the anesthesiologist administered 50 mL of 0.9% saline intravenously to patients in the control group 30 minutes before surgical incision Receives: Other: Placebo |
| Ketorolac Tromethamine | Experimental | In the operating room, the anesthesiologist administered ketorolac (30 mg) in 50 mL of 0.9 % saline intravenously to patients in the ketorolac group 30 minutes before surgical incision. (a single dose). Receives: Drug: Ketorolac Tromethamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain as measured by the Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 0 hours postoperatively (arrival at recovery room)
Pain as measured by the Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 1 hour postoperatively
Pain as measured by the Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 2 hours postoperatively
Pain as measured by the Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 4 hours postoperatively
Pain as measured by the Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 8 hours postoperatively
Pain as measured by the Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 12 hours postoperatively
Pain as measured by the Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 16 hours postoperatively
Pain as measured by the Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 24 hours postoperatively
Secondary outcomes (1)
tramadol consumption
The cumulative amounts of tramadol (mg) administered through the Patient-Controlled-Analgesia (PCA) device as a basal infusion and the incremental supplemental bolus required by the patient were documented at these time points.
Measured: at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2015 (estimated)
- Study startApr 2001
- Primary completionOct 2001
- Study completionNov 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Arquitecto Marcide
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Beatriz Nistal-Nuno, Oxford University Hospitals NHS Trust
- Investigators
- Beatriz Nistal-Nuño, MD, Principal investigator, Oxford University Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02642718
- Sponsor's protocol ID
- KP 359352
- Status last verified
- Jan 2016
- First submitted
- 19 Dec 2015
- Last updated
- 5 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-operative Ketorolac Administration Has no Pre-emptive Analgesic Effect Following Total Abdominal Hysterectomy
- ClinicalTrials.gov ID
- NCT02642718
- Acronym / sponsor ID
- KP 359352
- Conditions
- Pain
- Keywords
- preemptive analgesia, postoperative pain, NSAIDs, ketorolac, abdominal hysterectomy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Hospital Arquitecto MarcideUniversity, hospital or other
- Study start
- Apr 2001
- Primary completion
- Oct 2001 (actual)
- Study completion
- Nov 2001 (actual)
- First posted
- 30 Dec 2015 (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.
Background: Experimental models using short duration noxious stimuli have led to the concept of pre-emptive analgesia. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), has been shown to have a post-operative narcotic sparing effect when given pre-operatively and alternatively to not have this effect. This study was undertaken to determine whether a single intravenous dose of ketorolac would result in decreased post-operative pain and narcotic requirements.
Methods: In a double-blind, randomized controlled trial, 48 women undergoing abdominal hysterectomy were studied. Patients in the ketorolac group received 30 mg of intravenous ketorolac 30 minutes before surgical incision, while the control group received normal saline. The post-operative analgesia was performed with a continuous infusion of tramadol at 12 mg/hour with the possibility of a 10 mg bolus every 10 minutes. Pain was assessed using the Visual Analog Scale (VAS), tramadol consumption and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16 and 24 hours post-operatively. We quantified times to rescue analgesic (morphine), adverse effects and patient satisfaction.
Detailed description
Damage to tissues has been shown to provoke a magnified reaction to noxious stimuli, peripherally by diminishing the threshold of nociceptive afferent nerve terminals and centrally by augmenting the excitability of second-order sensory neurons in the spinal cord; later resulting in an amplification and extension of postoperative pain after surgery. Hence, much research has focused on procedures to avoid these central neuroplastic changes through the usage of preemptive analgesia.
Experimental models have conducted to the idea of 'preemptive analgesia' . The decrement of afferent nociceptive inputs to the spinal cord using analgesic techniques started before the initial painful stimulus avoids or attenuates the formation of spinal hyperexcitabilty and avoids the transformed processing of afferent input, leading to less postoperative pain. Whether such experimental models are applicable to the noxious circumstances occurring during surgery is controversial.
Although preemptive analgesia with different agents have been successful in experimental animals, conclusions from human studies remain in conflict. A diversity of agents have been analyzed for their conceivable preemptive analgesic effects: local anesthetics, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, opioids, magnesium, cytokine synthesis inhibitors, ketamine, and tricyclic antidepressants.
Scientific research enabling an understanding of the molecular mechanisms of nociception has disclosed a considerable function of cytokines and prostaglandins (PG). Hyperexcitability also appears peripherally in nerve endings at the location of surgical tissue damage and is mediated in part by prostaglandins. Evidence is accumulating that products of the cyclooxygenase pathway may be engaged in the elaboration of central sensitization. Drugs that block the formation of prostaglandins such as NSAIDs might therefore be assumed to avoid or minimize the formation of this peripheral and central hyperexcitability. Their central analgesic actions are effected by averting spinal prostaglandin synthesis and attenuating liberation of neurotransmitters from the primary afferent terminals and spinal interneurons.
Sporadic studies have established some considerable preemptive benefit of NSAIDs. As a result, the objective of this study was to ascertain the impact of a NSAID, ketorolac, on pain severity and analgesic requirement, in the early postoperative period.
Ketorolac is a nonselective NSAID that blocks cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) enzymes and as a result blocks the formation of prostaglandins attenuating the sensitization procedures. The antinociceptive and anti-inflammatory action of NSAIDs may be associated to the suppression of nitric oxide synthase activation, decreased generation of proinflammatory cytokines, and lipoxine activation. Consequently, this multidirectional activity indicates that there may be the probability of adjusting the nociception process by the employment of these drugs perioperatively.
To our knowledge, no prior controlled study has determined the effectiveness of preoperative intravenous ketorolac compared to placebo in patients who underwent abdominal hysterectomies. Thus, this clinical trial was conceived to explore the postoperative analgesic efficiency and opioid-sparing action of a single dose of intravenous ketorolac in contrast with placebo administered preoperatively.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboIn the operating room, the anesthesiologist administered 50 mL of 0.9% saline intravenously to patients in the control group 30 minutes before surgical incision |
| Ketorolac Tromethamine | Experimental | Drug: Ketorolac TromethamineIn the operating room, the anesthesiologist administered ketorolac (30 mg) in 50 mL of 0.9 % saline intravenously to patients in the ketorolac group 30 minutes before surgical incision. (a single dose). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- normal height and weight
- ASA class I, II, III
- elective surgery
- surgery time between 30-150 min
- understanding of the Visual Analog Scale (VAS)
Key exclusion criteria (11 listed)
- renal deterioration
- history of peptic ulceration
- asthma
- coagulopathy
- cognitive impairment
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 |
|---|---|---|
| Ketorolac TromethamineAlso: ketorolacIn the operating room, the anesthesiologist administered ketorolac (30 mg) in 50 mL of 0.9 % saline intravenously to patients in the ketorolac group 30 minutes before surgical incision (a single dose). | Drug | Ketorolac Tromethamine |
| PlaceboIn the operating room, the anesthesiologist administered 50 mL of 0.9 % saline intravenously to patients in the control group 30 minutes before surgical incision | Other | Placebo |
Primary outcome
Pain as measured by the Visual Analog Scale (VAS) score
Time frame: at 0 hours postoperatively (arrival at recovery room)
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Pain as measured by the Visual Analog Scale (VAS) score
Time frame: at 1 hour postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Pain as measured by the Visual Analog Scale (VAS) score
Time frame: at 2 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Pain as measured by the Visual Analog Scale (VAS) score
Time frame: at 4 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Pain as measured by the Visual Analog Scale (VAS) score
Time frame: at 8 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Pain as measured by the Visual Analog Scale (VAS) score
Time frame: at 12 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Pain as measured by the Visual Analog Scale (VAS) score
Time frame: at 16 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Pain as measured by the Visual Analog Scale (VAS) score
Time frame: at 24 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
1 secondary outcome
tramadol consumption
Time frame: at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2016.
- 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.
Beatriz Nistal-Nuño, MD principal investigator
Oxford University Hospitals NHS Trust
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketorolac Tromethamine in people with Pain, run by Hospital Arquitecto Marcide 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 7 inclusion and 11 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 5 Jan 2016. 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 Spain, United Kingdom. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pain as measured by the Visual Analog Scale (VAS) score (time frame: at 0 hours postoperatively (arrival at recovery room)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jan 2016.