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NCT Number: NCT04123873

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

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.

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Key information

Conditions

Pain, Acute Acute Pain Agnosia Analgesia Hip Arthropathy Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Pain Pain, Postoperative Pathologic Processes Pathological Conditions, Signs and Symptoms Perceptual Disorders Postoperative Complications Postoperative Pain Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Næstved-Slagelse-Ringsted Hospitals, Næstved, Danmark, Denmark

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Paracetamol

Drug

1g x 4 p.o.

Other names: Acetaminophen

Ibuprofen

Drug

400mg x 4 p.o.

Dexamethasone

Drug

24mg IV x 1 after induction om anaesthesia

Placebo oral capsules

Drug

p.o. x 4

Placebo IV

Drug

IV x 1

Primary outcomes

  1. Cumulative opioid consumption in the first 24 hours after surgery

    Time frame: 0-24 hours after end of 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

Secondary outcomes

  1. Pain scores during mobilisation 24h

    Time frame: 24 hours after end of surgery

    Pain scores (visual analogue scale (VAS 0-100 mm; no pain = 0; worst imaginable pain = 100)) with active 30 degrees flexion of the hip

  2. Pain scores at rest 24h

    Time frame: 24 hours after end of surgery

    Pain scores at rest (VAS 0-100 mm; no pain = 0; worst imaginable pain = 100)

  3. Maximum level of pain

    Time frame: 24 hours after end of surgery

    Maximum level of pain (VAS 0-100 mm No pain = 0; worst imaginable pain = 100) during walk of 5 meters

  4. Adverse events in the intervention period

    Time frame: From end of surgery + 24 hours

    Proportion of patients with one or more AEs in the intervention period

Other outcomes

  1. Serious adverse events within one year

    Time frame: Within 90 days

    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'

  2. Pain scores during mobilisation 6h

    Time frame: 6 hours after end of surgery

    Pain scores (visual analogue scale (VAS 0-100 mm; no pain = 0; worst imaginable pain = 100)) with active 30 degrees flexion of the hip

  3. Pain scores at rest 6h

    Time frame: 6 hours after end of surgery

    Pain scores at rest (VAS 0-100 mm; no pain = 0; worst imaginable pain = 100)

  4. Prevalence of nausea

    Time frame: 6 and 24 hours after end of surgery

    Prevalence of nausea, 6 and 24 hours after end of surgery

  5. Number of vomiting episodes

    Time frame: 0-24 after end of surgery. Reported by interview 24 hours after end of surgery

    The number of productive vomiting events (volume estimated over 10 ml) is recorded corresponding to the period 0-24 hours

  6. Consumption of ondansetron and dehydrobenzperidole

    Time frame: 0-24 hours after end of surgery

    Consumption of ondansetron and dehydrobenzperidole in mg

  7. Incidence of dizziness during 5 meter walk

    Time frame: 24 hours after end of surgery

    Incidence of dizziness during 5 meter walk 24 hours after surgery

  8. Blood loss

    Time frame: Intraoperatively

    Blood loss in ml during the surgical procedure

  9. Quality of sleep

    Time frame: 24 hours after end of surgery

    Quality of sleep (VAS 0-100 mm; worst possible sleep = 0; best possible sleep = 100) Worst possible sleep = 0; best possible sleep = 100

  10. Days alive and outside hospital within 90 days after surgery

    Time frame: Within 90 days after surgery

    Days alive and outside hospital within 90 days after surgery

  11. Oxford Hip Score at 90 days

    Time frame: At 90 days after surgery

    5-point Lipert-scale (no, mild, moderate, severe and extreme)

  12. Quality of life (EQ-5D-5L) at 90 days

    Time frame: At 90 days after surgery

    EuroQol five-dimensions 5 point Lipert scale (EQ-5D-5L)

  13. Opioid use at 90 days

    Time frame: Within 90 days after surgery

    Consumption of opioids within 90 days after surgery

  14. Serious adverse events within 1 year

    Time frame: Within one year after surgery

    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')

  15. Oxford Hip Score at one year

    Time frame: One year after surgery

    5-point Lipert-scale (no, mild, moderate, severe and extreme)

  16. Quality of life (EQ-5D-5L) at one year

    Time frame: One year after surgery

    EuroQol five-dimensions 5 point Lipert scale (EQ-5D-5L)

  17. Opioid use at one year

    Time frame: Within one year after surgery

    Consumption of opioids within one year after surgery

Sponsors and collaborators

Lead sponsor

Naestved Hospital

Other

Registry information

Official study 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

Acronym: RECIPE

Important dates

Study start
2020
Primary completion
2022
Study completion
2023
First posted
Oct 11, 2019
Registry last updated
Jun 1, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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