Clinical trial NCT04123873: Effect of Combinations of Paracetamol, Ibuprofen, and Dexamethasone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty
Official title: Effect of Combinations of Paracetamol, Ibuprofen, and Dexamethasone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty. The RECIPE Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Acute
Hip Arthropathy
Analgesia
Postoperative Pain
Keywords: RECIPE
Hip arthroplasty
Postoperative pain
Analgesia
Multimodal analgesia
Non-opioid analgesia
Acute pain
Lead sponsor: Naestved Hospital
Sponsor class: OTHER
First posted: 2019-10-11
Enrollment: 1060
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multimodal pain management is essential for recovery after surgery, aiming to target different pain mechanisms to minimize opioid usage and opioid-related adverse effects. Evidence for benefits and harms of various non-opioid analgesic combinations is, however, nearly non-existing, and large-scale trials are urgently needed.

Recently, the investigators have demonstrated that combining paracetamol and ibuprofen is superior to each single drug when assessing pain after hip replacement. Further improvement is needed, investigating additional non-opioid analgesics to this combination. Glucocorticoids have anti-emetic and analgesic properties, but evidence for analgesic efficacy in combination with paracetamol and ibuprofen is lacking.

The RECIPE trial is an investigator-initiated randomized, placebo-controlled, parallel, 4-group, blinded multicentre trial with 90-day follow-up investigating benefits and harms of different combinations of paracetamol, ibuprofen, and dexamethasone for patients undergoing total hip arthroplasty.

The primary outcome is total use of IV morphine 0-24 hours postoperatively. Secondary outcomes are pain (upon mobilisation, at rest, and during 5 m walk), and adverse events. Exploratory outcomes include quality of sleep, opioid-related adverse effects, serious adverse events (\< 90 days), and patient reported disability score and quality of life (at 90 days).

Based on sample-size calculations, 1060 patients are needed to detect a minimal clinically important difference in 24-hour morphine consumption of 8 mg, using a familywise type 1 error rate of 0.05 and a type 2 error rate of 0.2. The primary analyses will be based on the intention to treat population. More than six Danish university- and regional hospitals will participate in the trial.

With this trial the investigators expect to lay the foundation for the best postoperative multimodal analgesic regimen for both total hip arthroplasty and possibly other surgeries, thereby facilitating recovery for millions of future surgical patients worldwide.


Eligibility criteria: Inclusion Criteria:

* Scheduled for elective, unilateral, primary THA
* Age ≥ 18
* ASA 1-3
* BMI \> 18 and \< 40
* Negative urine HCG pregnancy test and use of anti-conception for women in the fertile age
* Give written informed consent to participate in the trial after having fully understood the contents of the protocol and restrictions

Exclusion Criteria:

* Patients who cannot cooperate with the trial
* Concomitant participation in another trial involving medication
* Patients who cannot understand or speak Danish
* Patients with allergy to medication used in the trial
* Patients with daily use of high dose opioid (\> oral morphine 30 mg/day or oxycodone 30 mg/day or tramadol 150 mg/day) or any use of other opioids including methadone and transdermal opioids.
* Patients with daily use of systemic glucocorticoids (within 3 months before the trial)
* Contraindications against ibuprofen or paracetamol, for example previous ulcer, known heart failure, known liver failure, or known renal failure (eGRF \< 60 ml/kg/1,73m2), known thrombocytopenia (\< 100 x 109/l); or against treatment with glucocorticoids
* Dysregulated diabetes (investigator's judgement)
* Patients suffering from alcohol and/or drug abuse - based on the investigator's judgement

Primary outcomes:
measure: Cumulative opioid consumption in the first 24 hours after surgery
timeFrame: 0-24 hours after end of surgery
Secondary outcomes:
measure: Pain scores during mobilisation 24h
timeFrame: 24 hours after end of surgery
measure: Pain scores at rest 24h
timeFrame: 24 hours after end of surgery
measure: Maximum level of pain
timeFrame: 24 hours after end of surgery
measure: Adverse events in the intervention period
timeFrame: From end of surgery + 24 hours
Other outcomes:
measure: Serious adverse events within one year
timeFrame: Within 90 days
measure: Pain scores during mobilisation 6h
timeFrame: 6 hours after end of surgery
measure: Pain scores at rest 6h
timeFrame: 6 hours after end of surgery
measure: Prevalence of nausea
timeFrame: 6 and 24 hours after end of surgery
measure: Number of vomiting episodes
timeFrame: 0-24 after end of surgery. Reported by interview 24 hours after end of surgery
measure: Consumption of ondansetron and dehydrobenzperidole
timeFrame: 0-24 hours after end of surgery
measure: Incidence of dizziness during 5 meter walk
timeFrame: 24 hours after end of surgery
measure: Blood loss
timeFrame: Intraoperatively
measure: Quality of sleep
timeFrame: 24 hours after end of surgery
measure: Days alive and outside hospital within 90 days after surgery
timeFrame: Within 90 days after surgery
measure: Oxford Hip Score at 90 days
timeFrame: At 90 days after surgery
measure: Quality of life (EQ-5D-5L) at 90 days
timeFrame: At 90 days after surgery
measure: Opioid use at 90 days
timeFrame: Within 90 days after surgery
measure: Serious adverse events within 1 year
timeFrame: Within one year after surgery
measure: Oxford Hip Score at one year
timeFrame: One year after surgery
measure: Quality of life (EQ-5D-5L) at one year
timeFrame: One year after surgery
measure: Opioid use at one year
timeFrame: Within one year after surgery
Locations:
city: Næstved
country: Denmark
facility: Næstved-Slagelse-Ringsted Hospitals
state: Danmark
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Hillerød
country: Denmark
facility: Hillerød Hospital
city: Køge
country: Denmark
facility: Køge Hospital
city: Odense
country: Denmark
facility: Odense University Hospital (OUH)
city: Svendborg
country: Denmark
facility: Svendborg Hospital
Study officials:
References:
citation: Steiness J, Hagi-Pedersen D, Lunn TH, Lindberg-Larsen M, Graungaard BK, Lundstrom LH, Lindholm P, Brorson S, Bieder MJ, Beck T, Skettrup M, von Cappeln AG, Thybo KH, Gasbjerg KS, Overgaard S, Jakobsen JC, Mathiesen O. Paracetamol, ibuprofen and dexamethasone for pain treatment after total hip arthroplasty: protocol for the randomised, placebo-controlled, parallel 4-group, blinded, multicentre RECIPE trial. BMJ Open. 2022 Sep 1;12(9):e058965. doi: 10.1136/bmjopen-2021-058965.