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

Postoperative Pain Clinical Trial

— RECIPE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04123873
• Other study ID #: SM1-JOAST-2019
• Status: Completed
• Phase: Phase 4
• Start date: March 5, 2020
• Est. completion date: February 15, 2023

Study information

• Verified date: May 2023
• Source: Naestved Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1060
• Est. completion date: February 15, 2023
• Est. primary completion date: November 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Pain
• Analgesia
• Hip Arthropathy
• Pain, Acute
• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Paracetamol
1g x 4 p.o.
• Ibuprofen
400mg x 4 p.o.
• Dexamethasone
24mg IV x 1 after induction om anaesthesia
• Placebo oral capsules
p.o. x 4
• Placebo IV
IV x 1

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Gentofte Hospital	Hellerup
Denmark	Hillerød Hospital	Hillerød
Denmark	Køge Hospital	Køge
Denmark	Næstved-Slagelse-Ringsted Hospitals	Næstved	Danmark
Denmark	Odense University Hospital (OUH)	Odense
Denmark	Svendborg Hospital	Svendborg

Sponsors (1)

Lead Sponsor	Collaborator
Naestved Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serious adverse events within one year	SAEs, including death, within 90 days after surgery defined as SAE (according to ICH-GCP-guidelines) except 'prolongation of hospitalisation' that has been modified to 'prolongation of hospitalization with =4 days'	Within 90 days
Other	Pain scores during mobilisation 6h	Pain scores (visual analogue scale (VAS 0-100 mm; no pain = 0; worst imaginable pain = 100)) with active 30 degrees flexion of the hip	6 hours after end of surgery
Other	Pain scores at rest 6h	Pain scores at rest (VAS 0-100 mm; no pain = 0; worst imaginable pain = 100)	6 hours after end of surgery
Other	Prevalence of nausea	Prevalence of nausea, 6 and 24 hours after end of surgery	6 and 24 hours after end of surgery
Other	Number of vomiting episodes	The number of productive vomiting events (volume estimated over 10 ml) is recorded corresponding to the period 0-24 hours	0-24 after end of surgery. Reported by interview 24 hours after end of surgery
Other	Consumption of ondansetron and dehydrobenzperidole	Consumption of ondansetron and dehydrobenzperidole in mg	0-24 hours after end of surgery
Other	Incidence of dizziness during 5 meter walk	Incidence of dizziness during 5 meter walk 24 hours after surgery	24 hours after end of surgery
Other	Blood loss	Blood loss in ml during the surgical procedure	Intraoperatively
Other	Quality of sleep	Quality of sleep (VAS 0-100 mm; worst possible sleep = 0; best possible sleep = 100) Worst possible sleep = 0; best possible sleep = 100	24 hours after end of surgery
Other	Days alive and outside hospital within 90 days after surgery	Days alive and outside hospital within 90 days after surgery	Within 90 days after surgery
Other	Oxford Hip Score at 90 days	5-point Lipert-scale (no, mild, moderate, severe and extreme)	At 90 days after surgery
Other	Quality of life (EQ-5D-5L) at 90 days	EuroQol five-dimensions 5 point Lipert scale (EQ-5D-5L)	At 90 days after surgery
Other	Opioid use at 90 days	Consumption of opioids within 90 days after surgery	Within 90 days after surgery
Other	Serious adverse events within 1 year	Proportion of participants with one or more serious adverse events, including death, within one year after surgery, according to ICH-GCP guidelines[24] (except for 'prolongation of hospitalization' that has been modified to 'prolongation of hospitalization with =4 days')	Within one year after surgery
Other	Oxford Hip Score at one year	5-point Lipert-scale (no, mild, moderate, severe and extreme)	One year after surgery
Other	Quality of life (EQ-5D-5L) at one year	EuroQol five-dimensions 5 point Lipert scale (EQ-5D-5L)	One year after surgery
Other	Opioid use at one year	Consumption of opioids within one year after surgery	Within one year after surgery
Primary	Cumulative opioid consumption in the first 24 hours after surgery	Cumulative opioid consumption in units of intravenous morphine equivalents in the first 24 postoperative hours. This includes opioids administered as (a) patient-controlled analgesia (PCA); (b) supplemental opioid administered at the post-anaesthesia care unit the first hour after end of surgery (general anaesthesia) or the first hour after ceasing of spinal anaesthesia; and (c) any supplemental opioid given at the ward	0-24 hours after end of surgery
Secondary	Pain scores during mobilisation 24h	Pain scores (visual analogue scale (VAS 0-100 mm; no pain = 0; worst imaginable pain = 100)) with active 30 degrees flexion of the hip	24 hours after end of surgery
Secondary	Pain scores at rest 24h	Pain scores at rest (VAS 0-100 mm; no pain = 0; worst imaginable pain = 100)	24 hours after end of surgery
Secondary	Maximum level of pain	Maximum level of pain (VAS 0-100 mm No pain = 0; worst imaginable pain = 100) during walk of 5 meters	24 hours after end of surgery
Secondary	Adverse events in the intervention period	Proportion of patients with one or more AEs in the intervention period	From end of surgery + 24 hours

External Links

•   Trial website