Pain, AcutePhase 4RECIPENCT04123873
Effect of Combinations of Paracetamol, Ibuprofen, and Dexamethasone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty
A Phase 4 study testing Paracetamol, Ibuprofen and Dexamethasone in people with Pain, Acute and Hip Arthropathy, run by Naestved Hospital at 7 sites in Denmark.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Acute, Hip Arthropathy, Analgesia
- What is being tested?
- Paracetamol, Ibuprofen and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,060 participants
- Where
- 7 sitesDenmark
- Study dates
- 5 Mar 2020to 15 Feb 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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 locations and contacts
7 sites in 1 country.
7 sites in 1 country
Denmark7 sites
Bispebjerg Hospital
Copenhagen, 2400
Gentofte Hospital
Hellerup, 2900
Hillerød Hospital
Hillerød, 3400
Køge Hospital
Køge, 4600
Næstved-Slagelse-Ringsted Hospitals
Næstved, Danmark, 4700
Odense University Hospital (OUH)
Odense, 5000
Svendborg Hospital
Svendborg, 5700
About this study
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
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.
Read more
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.
- Conditions
- Pain, Acute, Hip Arthropathy, Analgesia, Postoperative Pain
- Being tested
- Paracetamol, Ibuprofen, Dexamethasone, Placebo oral capsules, Placebo IV
- Keywords
- RECIPE, Hip arthroplasty, Postoperative pain, Analgesia, Multimodal analgesia, Non-opioid analgesia, Acute pain
- Medical subject headings
- Acute Pain, Agnosia, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParacetamolDrug
Also called Acetaminophen
1g x 4 p.o.
IbuprofenDrug
400mg x 4 p.o.
DexamethasoneDrug
24mg IV x 1 after induction om anaesthesia
Placebo oral capsulesDrug
p.o. x 4
Placebo IVDrug
IV x 1
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | 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 Receives: Drug: Paracetamol; Drug: Ibuprofen; Drug: Placebo IV |
| Group B | Experimental | 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 Receives: Drug: Paracetamol; Drug: Dexamethasone; Drug: Placebo oral capsules |
| Group C | Experimental | 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 Receives: Drug: Ibuprofen; Drug: Dexamethasone; Drug: Placebo oral capsules |
| Group D | Experimental | 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 Receives: Drug: Paracetamol; Drug: Ibuprofen; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 0-24 hours after end of surgery
Secondary outcomes (4)
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
Measured: 24 hours after end of surgery
Pain scores at rest 24h
Pain scores at rest (VAS 0-100 mm; no pain = 0; worst imaginable pain = 100)
Measured: 24 hours after end of surgery
Maximum level of pain
Maximum level of pain (VAS 0-100 mm No pain = 0; worst imaginable pain = 100) during walk of 5 meters
Measured: 24 hours after end of surgery
Adverse events in the intervention period
Proportion of patients with one or more AEs in the intervention period
Measured: From end of surgery + 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2019
- Study start5 Mar 2020
- Primary completion15 Nov 2022
- Study completion15 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pain, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,060 participants (actual)
Sponsor and investigators
- Lead sponsor
- Naestved Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04123873
- Sponsor's protocol ID
- SM1-JOAST-2019
- Acronym
- RECIPE
- Status last verified
- May 2023
- First submitted
- 27 Sep 2019
- Last updated
- 1 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Steiness J, Hagi-Pedersen D, Lunn TH, Overgaard S, Brorson S, Graungaard BK, Lindberg-Larsen M, Varnum C, Lundstrom LH, Beck T, Skettrup M, Pedersen NA, Bieder MJ, von Cappeln AG, Pleckaitiene L, Lindholm P, Bukhari SSH, Derby CB, Nielsen MG, Exsteen OW, Vinstrup LO, Thybo KH, Gasbjerg KS, Norskov AK, Jakobsen JC, Mathiesen O; RECIPE trial group. Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial. Lancet Rheumatol. 2024 Apr;6(4):e205-e215. doi: 10.1016/S2665-9913(24)00020-1. Epub 2024 Mar 5.
PubMed 38458208Steiness 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.
PubMed 36190737
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04123873
- Acronym / sponsor ID
- RECIPE / SM1-JOAST-2019
- Conditions
- Pain, Acute, Hip Arthropathy, Analgesia, Postoperative Pain
- Keywords
- RECIPE, Hip arthroplasty, Postoperative pain, Analgesia, Multimodal analgesia, Non-opioid analgesia, Acute pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,060 participants (actual)
- Lead sponsor
- Naestved HospitalUniversity, hospital or other
- Study start
- 5 Mar 2020 (actual)
- Primary completion
- 15 Nov 2022 (actual)
- Study completion
- 15 Feb 2023 (actual)
- First posted
- 11 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Paracetamol, Drug: Ibuprofen, Drug: Placebo IVParacetamol 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 |
| Group B | Experimental | Drug: Paracetamol, Drug: Dexamethasone, Drug: Placebo oral capsulesParacetamol 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 |
| Group C | Experimental | Drug: Ibuprofen, Drug: Dexamethasone, Drug: Placebo oral capsulesPlacebo (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 |
| Group D | Experimental | Drug: Paracetamol, Drug: Ibuprofen, Drug: DexamethasoneParacetamol 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParacetamolAlso: Acetaminophen1g x 4 p.o. | Drug | Group A, Group B, Group D |
| Ibuprofen400mg x 4 p.o. | Drug | Group A, Group C, Group D |
| Dexamethasone24mg IV x 1 after induction om anaesthesia | Drug | Group B, Group C, Group D |
| Placebo oral capsulesp.o. x 4 | Drug | Group B, Group C |
| Placebo IVIV x 1 | Drug | Group A |
Primary outcome
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
4 secondary outcomes
Pain scores during mobilisation 24h
Time frame: 24 hours after end of surgery
Pain scores at rest 24h
Time frame: 24 hours after end of surgery
Maximum level of pain
Time frame: 24 hours after end of surgery
Adverse events in the intervention period
Time frame: From end of surgery + 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2023.
- Derived from this study: PubMed 38458208Steiness J, Hagi-Pedersen D, Lunn TH, Overgaard S, Brorson S, Graungaard BK, Lindberg-Larsen M, Varnum C, Lundstrom LH, Beck T, Skettrup M, Pedersen NA, Bieder MJ, von Cappeln AG, Pleckaitiene L, Lindholm P, Bukhari SSH, Derby CB, Nielsen MG, Exsteen OW, Vinstrup LO, Thybo KH, Gasbjerg KS, Norskov AK, Jakobsen JC, Mathiesen O; RECIPE trial group. Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial. Lancet Rheumatol. 2024 Apr;6(4):e205-e215. doi: 10.1016/S2665-9913(24)00020-1. Epub 2024 Mar 5.
- Derived from this study: PubMed 36190737Steiness 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.
- Trial websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Paracetamol, Ibuprofen and Dexamethasone in people with Pain, Acute and Hip Arthropathy, run by Naestved Hospital at 7 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative opioid consumption in the first 24 hours after surgery (time frame: 0-24 hours after end of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04123873, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2023.