Reduce Nonsteroidal Antiinflammatory Drugs Doses for Analgesia After Sternotomy

Cardiac Surgery Clinical Trial

— LoDoNSAID  

Official title:

Reduce Nonsteroidal Antiinflammatory Drugs Doses for Analgesia After Sternotomy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02180087
• Other study ID #: CHU-0198
• Secondary ID: 2013-003878-27
• Status: Recruiting
• Phase: Phase 2
• First received: July 1, 2014
• Last updated: July 1, 2014
• Start date: February 2014
• Est. completion date: September 2015

Study information

• Verified date: July 2014
• Source: University Hospital, Clermont-Ferrand
• Contact: Patrick LACARIN
• Phone: 04 73 75 11 95
• Email: placarin[@]chu-clermontferrand.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical 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).

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Surgery
• Pain, Postoperative
• Post-operative Pain

Intervention

Drug:
• Ketoprofen

Locations

Country	Name	City	State
France	CHU de Clermont-Ferrand	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Demographic criteria		at day 1	No
Secondary	Quantity of sufentanil administered intraoperatively		at day 1	No
Secondary	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	No
Secondary	Total morphine consumption		from H0 to H0+48 hours	No
Secondary	Blood gas monitoring 3 times a day		from H0 to H0+48 hours	No
Secondary	Time of removal of drains after surgery		at day 1	No
Secondary	Resumption of transit characterized by the first gas time after surgery.		at day 1	No
Secondary	Nausea occurrence (number of episodes) assessed every 4 hours		from H0 to H0 +48 hours	No
Secondary	Vomiting occurrence (number of episodes) assessed every 4 hours		from H0 to H0 +48 hours	No
Secondary	Effective Duration of stay in the Intensive Care Unit		at day 1	No
Secondary	Patient satisfaction for its first mobilization assessed by simple scale Likert		at H0+ 48 hours	No
Secondary	Occurrence of the following complications: Renal respiratory cardiac Neurological infectious Hemorrhagic		From H0 to H0+48 hours	No
Secondary	Any readmission to the intensive care unit in the two weeks following the surgery		at day 7	No