Reduce Nonsteroidal Antiinflammatory Drugs Doses for Analgesia After Sternotomy (LoDoNSAID)

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.

Study Overview

• Status: Unknown
• Conditions: Cardiac Surgery; Post-operative Pain
• Intervention / Treatment: Drug: Ketoprofen

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Recruiting
    • CHU de Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• Age over 75 years
• Renal insufficiency (MDRD <60 ml / min)
• Hepatic Insufficiency
• Congestive heart failure (EF <40%)
• Insulin-requiring diabetes
• Preoperative coagulation trouble
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo group; 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	Drug: Ketoprofen
Other: ketopofen quarter dose; 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.	Drug: Ketoprofen
Other: ketoprofen half-dose; 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.	Drug: Ketoprofen
Other: Ketoprofen full dose; 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	Drug: Ketoprofen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	At the first 48 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographic criteria		at day 1
Quantity of sufentanil administered intraoperatively		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)	at day 1
Total morphine consumption		from H0 to H0+48 hours
Blood gas monitoring 3 times a day		from H0 to H0+48 hours
Time of removal of drains after surgery		at day 1
Resumption of transit characterized by the first gas time after surgery.		at day 1
Nausea occurrence (number of episodes) assessed every 4 hours		from H0 to H0 +48 hours
Vomiting occurrence (number of episodes) assessed every 4 hours		from H0 to H0 +48 hours
Effective Duration of stay in the Intensive Care Unit		at day 1
Patient satisfaction for its first mobilization assessed by simple scale Likert		at H0+ 48 hours
Occurrence of the following complications: Renal respiratory cardiac Neurological infectious Hemorrhagic		From H0 to H0+48 hours
Any readmission to the intensive care unit in the two weeks following the surgery		at day 7

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): August 1, 2015
• Study Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: July 1, 2014
• First Submitted That Met QC Criteria: July 1, 2014
• First Posted (Estimate): July 2, 2014

Study Record Updates

• Last Update Posted (Estimate): July 2, 2014
• Last Update Submitted That Met QC Criteria: July 1, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Post-operative pain; Cardiac surgery; Kétoprofène; Minimum analgesic dose; Morphin consumption; Morphin secondary effects; Patient comfort and satisfaction; Renal fonction
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketoprofen
• Other Study ID Numbers: CHU-0198; 2013-003878-27