Cardiac SurgeryPhase 2LoDoNSAIDNCT02180087
Reduce Nonsteroidal Antiinflammatory Drugs Doses for Analgesia After Sternotomy
A Phase 2 study testing Ketoprofen in people with Cardiac Surgery and Post-operative Pain, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial summary
Currently, the management of pain after cardiac surgery is based on the concept of multimodal analgesia: Combined use of non-opioid analgesics associated with morphine intravenous analgesia by a system controlled by the patient (patient-controlled analgesia-PCA). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cardiac Surgery, Post-operative Pain
- What is being tested?
- Ketoprofen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2014to Sep 2015
- Phase
- Phase 2
- 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
- Patients scheduled for a cardiac surgery (Coronary artery bypass graft, valve replacement)
- Age over 18 years
- Weight between 60 and 100 kg
- Absence of criteria for non-inclusion
Who cannot join
- Age over 75 years
- Renal insufficiency (MDRD <60 ml / min)
- Hepatic Insufficiency
- Congestive heart failure (EF <40%)
- Insulin-requiring diabetes
- Preoperative coagulation trouble
Show all 12Show fewer
- History of peptic ulcer or gastrointestinal bleeding
- Allergy to NSAIDs
- Surgery in emergency, aorta surgery, heart transplantation
- Peptic ulcer scalable, history of peptic ulcer or recurrent bleeding (2 or more distinct episodes of bleeding or ulceration objectified)
- Pregnant or lactating women
- Major protected
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
CHU de Clermont-Ferrand
Clermont-Ferrand, 63003
Patrick LACARIN, 04 73 75 11 95, placarin@chu-clermontferrand.fr
About this study
Currently, the management of pain after cardiac surgery is based on the concept of multimodal analgesia: Combined use of non-opioid analgesics associated with morphine intravenous analgesia by a system controlled by the patient (patient-controlled analgesia-PCA).
The combination of paracetamol and morphine PCA is very effective on pain at rest, but is limited on pain mobilization and causes the problem of side effects associated with opioid (overdose, sedation, respiratory depression, gastrointestinal intolerance, urinary retention ...) which are contributing factors to increase the length of stay in Intensive Care Unit, an additional cost of care and an increase postoperative morbidity and mortality.
Read more
Methods that have proved their effectiveness on pain and mobilization used in postoperative cardiac surgery are: anti-inflammatory drugs (NSAIDs) and / or loco-regional analgesia techniques. NSAIDs enhance analgesia produced by PCA Morphine and allow a reduction in morphine consumption, improved postoperative pain, decreased sedation and decreased postoperative morbidity and mortality.
Adverse effects of NSAIDs are commensurate with their time and exposure dose. Consequently, NSAIDs, in the absence of against-indications, should always be prescribed and used at the lowest effective dose and for the shortest possible time.
Some studies have suggested that lower doses of NSAIDs didn't appear to affect their effectiveness. At present, the investigators have no studies that address the hypothesis from which minimum dose of ketoprofen analgesic effect is obtained.
The investigators hypothesis is that lower dose ketoprofen may have efficacy on pain in the postoperative mobilization of cardiac surgery. The investigators want to find, in their study, this "optimal" ketoprofen dose which would be the minimum dose for clinical efficacy demonstrated dose.
This optimal dose could reduce the number of adverse effects of NSAIDs, but their study will probably not have enough power to prove it. NSAID use at these low doses, in postoperative cardiac surgery, could be extended to patient populations most at risk or for a duration longer than 48 hours.
Read the detailed description
To answer this hypothesis the investigators will consider starting a study of four groups of patients where appropriate doses to patient weight gradually increasing ketoprofen will be used in seeking the minimum effective dose.
Four groups will be determined by randomization. In all these groups, analgesia will be supplemented by a systematic standard self-administered treatment with morphine and paracetamol.
- Group 1 : Placebo group (P). 0 mg/kg ketoprofen IV every 6 hours for 48 hours (or 0 mg/kg every 24 hours) for 48 hours.
- Group 2 : "Ketoprofen quarter dose" (K ¼). 0,125 mg/kg ketoprofen IV every 6 hours (0,5 mg/kg every 24 hours) for 48 hours.
- Group 3 : "Ketoprofen half-dose" (K ½). 0,25 mg/kg ketoprofen IV every 6 hours (1 mg/kg every 24 hours) for 48 hours.
- Group 4 : "Ketoprofen full dose" (KPD). 0,5 mg/kg ketoprofen IV every 6 hours (or 2 mg/kg every 24 hours) for 48 hours.
- Conditions
- Cardiac Surgery, Post-operative Pain
- Being tested
- Ketoprofen
- Keywords
- Cardiac surgery, Post-operative pain, Kétoprofène, Minimum analgesic dose, Morphin consumption, Morphin secondary effects, Patient comfort and satisfaction, Renal fonction
- Medical subject headings
- Pain, Postoperative, Personal Satisfaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetoprofenDrug
| Study group | Role | What they receive |
|---|---|---|
| placebo group | Placebo comparator | Group 1 : Placebo group (P). 0 mg/kg ketoprofen IV every 6 hours for 48 hours (or 0 mg/kg every 24 hours) for 48 hours Receives: Drug: Ketoprofen |
| ketopofen quarter dose | Other | Group 2 : "Ketoprofen quarter dose" (K ¼). 0,125 mg/kg ketoprofen IV every 6 hours (0,5 mg/kg every 24 hours) for 48 hours. Receives: Drug: Ketoprofen |
| ketoprofen half-dose | Other | Group 3 : "Ketoprofen half-dose" (K ½). 0,25 mg/kg ketoprofen IV every 6 hours (1 mg/kg every 24 hours) for 48 hours. Receives: Drug: Ketoprofen |
| Ketoprofen full dose | Other | Group 4 : "Ketoprofen full dose" (KPD). 0,5 mg/kg ketoprofen IV every 6 hours (or 2 mg/kg every 24 hours) for 48 hours Receives: Drug: Ketoprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain at the mobilization
Pain at the mobilization of the first 48 hours postoperatively, measured every 4 hours by simple numerical scale or VAS (0: no pain to 10: unbearable pain)
Measured: At the first 48 hours postoperatively
Secondary outcomes (13)
Demographic criteria
Measured: at day 1
Quantity of sufentanil administered intraoperatively
Measured: at day 1
Pain at rest measured by Visual Analogue Scale
Pain at rest measured every 4 hours from H0+4 hours to H+48 hours by Visual Analogue Scale (H0 : sedation stop time, 1 hour before waking)
Measured: at day 1
Total morphine consumption
Measured: from H0 to H0+48 hours
Blood gas monitoring 3 times a day
Measured: from H0 to H0+48 hours
Time of removal of drains after surgery
Measured: at day 1
Resumption of transit characterized by the first gas time after surgery.
Measured: at day 1
Nausea occurrence (number of episodes) assessed every 4 hours
Measured: from H0 to H0 +48 hours
Vomiting occurrence (number of episodes) assessed every 4 hours
Measured: from H0 to H0 +48 hours
Effective Duration of stay in the Intensive Care Unit
Measured: at day 1
Patient satisfaction for its first mobilization assessed by simple scale Likert
Measured: at H0+ 48 hours
Occurrence of the following complications: Renal respiratory cardiac Neurological infectious Hemorrhagic
Measured: From H0 to H0+48 hours
Any readmission to the intensive care unit in the two weeks following the surgery
Measured: at day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2014 (estimated)
- Study startFeb 2014
- Primary completionAug 2015 (estimated)
- Study completionSep 2015 (estimated)
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 Cardiac SurgeryStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vedat ELJEZI, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02180087
- Sponsor's protocol ID
- CHU-0198
- Other IDs
- 2013-003878-27
- Acronym
- LoDoNSAID
- Status last verified
- Jul 2014
- First submitted
- 1 Jul 2014
- Last updated
- 2 Jul 2014
- Results posted
- No
Publications
Eljezi V, Biboulet C, Boby H, Schoeffler P, Pereira B, Duale C. The Dose-Dependent Effects of Ketoprofen on Dynamic Pain after Open Heart Surgery. Pain Physician. 2017 Sep;20(6):509-520.
PubMed 28934782
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduce Nonsteroidal Antiinflammatory Drugs Doses for Analgesia After Sternotomy
- ClinicalTrials.gov ID
- NCT02180087
- Acronym / sponsor ID
- LoDoNSAID / CHU-0198
- Conditions
- Cardiac Surgery, Post-operative Pain
- Keywords
- Cardiac surgery, Post-operative pain, Kétoprofène, Minimum analgesic dose, Morphin consumption, Morphin secondary effects, Patient comfort and satisfaction, Renal fonction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Aug 2015 (estimated)
- Study completion
- Sep 2015 (estimated)
- First posted
- 2 Jul 2014 (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.
Currently, the management of pain after cardiac surgery is based on the concept of multimodal analgesia: Combined use of non-opioid analgesics associated with morphine intravenous analgesia by a system controlled by the patient (patient-controlled analgesia-PCA).
The combination of paracetamol and morphine PCA is very effective on pain at rest, but is limited on pain mobilization and causes the problem of side effects associated with opioid (overdose, sedation, respiratory depression, gastrointestinal intolerance, urinary retention ...) which are contributing factors to increase the length of stay in Intensive Care Unit, an additional cost of care and an increase postoperative morbidity and mortality.
Methods that have proved their effectiveness on pain and mobilization used in postoperative cardiac surgery are: anti-inflammatory drugs (NSAIDs) and / or loco-regional analgesia techniques. NSAIDs enhance analgesia produced by PCA Morphine and allow a reduction in morphine consumption, improved postoperative pain, decreased sedation and decreased postoperative morbidity and mortality.
Adverse effects of NSAIDs are commensurate with their time and exposure dose. Consequently, NSAIDs, in the absence of against-indications, should always be prescribed and used at the lowest effective dose and for the shortest possible time.
Some studies have suggested that lower doses of NSAIDs didn't appear to affect their effectiveness. At present, the investigators have no studies that address the hypothesis from which minimum dose of ketoprofen analgesic effect is obtained.
The investigators hypothesis is that lower dose ketoprofen may have efficacy on pain in the postoperative mobilization of cardiac surgery. The investigators want to find, in their study, this "optimal" ketoprofen dose which would be the minimum dose for clinical efficacy demonstrated dose.
This optimal dose could reduce the number of adverse effects of NSAIDs, but their study will probably not have enough power to prove it. NSAID use at these low doses, in postoperative cardiac surgery, could be extended to patient populations most at risk or for a duration longer than 48 hours.
Detailed description
To answer this hypothesis the investigators will consider starting a study of four groups of patients where appropriate doses to patient weight gradually increasing ketoprofen will be used in seeking the minimum effective dose.
Four groups will be determined by randomization. In all these groups, analgesia will be supplemented by a systematic standard self-administered treatment with morphine and paracetamol.
- Group 1 : Placebo group (P). 0 mg/kg ketoprofen IV every 6 hours for 48 hours (or 0 mg/kg every 24 hours) for 48 hours.
- Group 2 : "Ketoprofen quarter dose" (K ¼). 0,125 mg/kg ketoprofen IV every 6 hours (0,5 mg/kg every 24 hours) for 48 hours.
- Group 3 : "Ketoprofen half-dose" (K ½). 0,25 mg/kg ketoprofen IV every 6 hours (1 mg/kg every 24 hours) for 48 hours.
- Group 4 : "Ketoprofen full dose" (KPD). 0,5 mg/kg ketoprofen IV every 6 hours (or 2 mg/kg every 24 hours) for 48 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| placebo group | Placebo comparator | Drug: KetoprofenGroup 1 : Placebo group (P). 0 mg/kg ketoprofen IV every 6 hours for 48 hours (or 0 mg/kg every 24 hours) for 48 hours |
| ketopofen quarter dose | Other | Drug: KetoprofenGroup 2 : "Ketoprofen quarter dose" (K ¼). 0,125 mg/kg ketoprofen IV every 6 hours (0,5 mg/kg every 24 hours) for 48 hours. |
| ketoprofen half-dose | Other | Drug: KetoprofenGroup 3 : "Ketoprofen half-dose" (K ½). 0,25 mg/kg ketoprofen IV every 6 hours (1 mg/kg every 24 hours) for 48 hours. |
| Ketoprofen full dose | Other | Drug: KetoprofenGroup 4 : "Ketoprofen full dose" (KPD). 0,5 mg/kg ketoprofen IV every 6 hours (or 2 mg/kg every 24 hours) for 48 hours |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients scheduled for a cardiac surgery (Coronary artery bypass graft, valve replacement)
- Age over 18 years
- Weight between 60 and 100 kg
- Absence of criteria for non-inclusion
Key exclusion criteria (12 listed)
- Age over 75 years
- Renal insufficiency (MDRD <60 ml / min)
- Hepatic Insufficiency
- Congestive heart failure (EF <40%)
- Insulin-requiring diabetes
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 |
|---|---|---|
| Ketoprofen | Drug | Ketoprofen full dose, ketopofen quarter dose, ketoprofen half-dose, placebo group |
Primary outcome
Pain at the mobilization
Time frame: At the first 48 hours postoperatively
Pain at the mobilization of the first 48 hours postoperatively, measured every 4 hours by simple numerical scale or VAS (0: no pain to 10: unbearable pain)
13 secondary outcomes
Demographic criteria
Time frame: at day 1
Quantity of sufentanil administered intraoperatively
Time frame: at day 1
Pain at rest measured by Visual Analogue Scale
Time frame: at day 1
Total morphine consumption
Time frame: from H0 to H0+48 hours
Blood gas monitoring 3 times a day
Time frame: from H0 to H0+48 hours
Time of removal of drains after surgery
Time frame: at day 1
Resumption of transit characterized by the first gas time after surgery.
Time frame: at day 1
Nausea occurrence (number of episodes) assessed every 4 hours
Time frame: from H0 to H0 +48 hours
Vomiting occurrence (number of episodes) assessed every 4 hours
Time frame: from H0 to H0 +48 hours
Effective Duration of stay in the Intensive Care Unit
Time frame: at day 1
Patient satisfaction for its first mobilization assessed by simple scale Likert
Time frame: at H0+ 48 hours
Occurrence of the following complications: Renal respiratory cardiac Neurological infectious Hemorrhagic
Time frame: From H0 to H0+48 hours
Any readmission to the intensive care unit in the two weeks following the surgery
Time frame: at day 7
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2014.
- Derived from this study: PubMed 28934782Eljezi V, Biboulet C, Boby H, Schoeffler P, Pereira B, Duale C. The Dose-Dependent Effects of Ketoprofen on Dynamic Pain after Open Heart Surgery. Pain Physician. 2017 Sep;20(6):509-520.
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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.
Vedat ELJEZI principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketoprofen in people with Cardiac Surgery and Post-operative Pain, run by University Hospital, Clermont-Ferrand at 1 site in France.
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 4 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: status not confirmed, as of the sponsor's last update on 2 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Patrick LACARIN (04 73 75 11 95, placarin@chu-clermontferrand.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain at the mobilization (time frame: At the first 48 hours postoperatively). 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 NCT02180087, 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 2 Jul 2014.