Effect of Combinations of Paracetamol, Ibuprofen, and Dexamethasone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty (RECIPE)

Naestved Hospital

Status and phase: Completed; Phase 4

Conditions: Postoperative Pain; Hip Arthropathy; Pain, Acute; Analgesia

Treatments: Drug: Placebo IV; Drug: Dexamethasone; Drug: Placebo oral capsules; Drug: Paracetamol; Drug: Ibuprofen

Study type: Interventional

Funder types: Other

Identifiers

NCT04123873

SM1-JOAST-2019

Details and patient eligibility

About

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.

Enrollment: 1,060 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,060 participants in 4 patient groups

Group A

Experimental group

Description:

Paracetamol 1000 mg + Ibuprofen 400 mg administered orally 1 hour before surgery and given with 6-hour intervals to a total of 4 times the first postoperative day. Plus placebo (matching DXM) IV administered after induction of anaesthesia

Treatment:

Drug: Ibuprofen

Drug: Paracetamol

Drug: Placebo IV

Group B

Experimental group

Description:

Paracetamol 1000 mg and placebo (matching ibuprofen) orally 1 hour before surgery and given with 6-hour intervals to a total of 4 times the first postoperative day. Plus DXM 24 mg IV after induction of anaesthesia

Treatment:

Drug: Paracetamol

Drug: Placebo oral capsules

Drug: Dexamethasone

Group C

Experimental group

Description:

Placebo (matching paracetamol) + ibuprofen 400 mg orally 1 hour before surgery and given with 6-hour intervals to a total of 4 times the first postoperative day. Plus DXM 24 mg IV after induction of anaesthesia

Treatment:

Drug: Ibuprofen

Drug: Placebo oral capsules

Drug: Dexamethasone

Group D

Experimental group

Description:

Paracetamol 1000 mg + ibuprofen 400 mg orally 1 hour before surgery and given with 6-hour intervals to a total of 4 times the first postoperative day. Plus DXM 24 mg IV after induction of anaesthesia

Treatment:

Drug: Ibuprofen

Drug: Paracetamol

Drug: Dexamethasone