PAracetamol and NSAID in Combination: A Randomised, Blinded, Parallel, 4-group Clinical Trial

NCT02571361 | Completed Phase 4

• 2 other identifiers: SM2-KHT-2015 - v22015-002239-16
• Study Type: interventional
• Target: 556
• Locations: 1 country
• Sites: 6

Brief Summary

Trial name: PAracetamol and NSAID in combination: A randomised, blinded, parallel, 4-group clinical trial Trial acronym: PANSAID Background: Effective postoperative pain management is essential for the well-being and rehabilitation of the surgical patient. No "gold standard" exists after total hip arthroplasty (THA) and combinations of different non-opioid medications are used with virtually no evidence for additional analgesic efficacy compared to monotherapy. Objectives: The objective of this trial is to investigate the analgesic effects and safety of paracetamol and ibuprofen and their combination in different dosages after THA. Intervention: Patients are randomised to 4 groups: A) paracetamol 1 g x 4 and ibuprofen 400 mg x 4; B) paracetamol 1 g x 4 and placebo (ibuprofen); C) placebo (paracetamol) and ibuprofen 400 mg x 4; and D) paracetamol 0,5 g x 4 and ibuprofen 200 mg. Design: Placebo controlled, parallel 4-group, multicentre trial with adequate centralised computer-generated allocation sequence and allocation concealment with varying block size and stratification by site. Blinding of assessor, investigator, caregivers, patients, and statisticians. Sample size: 556 eligible patients are needed to detect a difference of 10 mg morphine the first postoperative day with a standard deviation of 20 mg and a type 1 error rate of 0,004 (two-sided) and a type 2 error rate of 0,10.

Conditions

Pain, Postoperative

Keywords

Acetaminophen; Ibuprofen; Arthroplasty, Replacement, Hip

Outcome Measures

Primary Outcomes (2)

• Morphine consumption the first 24 hours postoperatively

  Total need for morphine administered as BOTH patient controlled analgesia (PCA) for the first 24 hours postoperatively AND supplemental morphine administered at the post-anaesthesia unit the first hour postoperatively. Bolus 2.0 mg; lockout: 10 min

  0-24 hours postoperatively

• Serious adverse events

  Serious adverse events, including death, within 90 days after surgery defined as SAE (according to ICH-GCP-guidelines) except "prolongation of hospitalisation"

  0-90 days postoperatively

Secondary Outcomes (5)

• Pain during movement at 6 hours postoperatively (visual analogue scale)

  6 hours postoperatively

• Pain during movement at 24 hours postoperatively (visual analogue scale)

  24 hours postoperatively

• Pain at rest at 6 hours postoperatively (visual analogue scale)

  6 hours postoperatively

• Pain at rest at 24 hours postoperatively (visual analogue scale)

  24 hours postoperatively

• Adverse events

  0-24 hours postoperatively

Other Outcomes (10)

• Nausea at 6 hours postoperatively (Verbal rating scale)

  6 hours postoperatively

• Nausea at 24 hours postoperatively (Verbal rating scale)

  24 hours postoperatively

• Vomiting the first 24 hours postoperatively

  0-24 hours postoperatively

Study Arms (4)

Treatment A:

ACTIVE COMPARATOR

Paracetamol 1g + ibuprofen 400 mg orally starting 1 hour before surgery and given with 6-hour intervals (+/- 1 hour) i.e. a total of 4 times the first 24 hours postoperative.

Drug: Paracetamol (1g x 4); Drug: Ibuprofen (400 mg x 4)

Treatment B:

ACTIVE COMPARATOR

Paracetamol 1g + placebo orally starting 1 hour before surgery and given with 6-hour intervals (+/- 1 hour) i.e. a total of 4 times the first 24 hours postoperative.

Drug: Paracetamol (1g x 4); Drug: Placebo (x4)

Treatment C:

ACTIVE COMPARATOR

Placebo + ibuprofen 400 mg orally starting 1 hour before surgery and given with 6-hour intervals (+/- 1 hour) i.e. a total of 4 times the first 24 hours postoperative.

Drug: Ibuprofen (400 mg x 4); Drug: Placebo (x4)

Treatment D:

ACTIVE COMPARATOR

Paracetamol 0,5 g + ibuprofen 200 mg orally starting 1 hour before surgery and given with 6-hour intervals (+/- 1 hour) i.e. a total of 4 times the first 24 hours postoperative.

Drug: Paracetamol (0,5 g x 4); Drug: Ibuprofen (200 mg x 4)

Interventions

Paracetamol (1g x 4) DRUG

Dose of 1 g given in 6 hour intervals the first 24 hours postoperatively

Also known as: Acetaminophen

Treatment A:; Treatment B:

Ibuprofen (400 mg x 4) DRUG

Dose of 400 mg given in 6 hour intervals the first 24 hours postoperatively

Treatment A:; Treatment C:

Paracetamol (0,5 g x 4) DRUG

Dose of 0,5 g given in 6 hour intervals the first 24 hours postoperatively

Also known as: Acetaminophen

Treatment D:

Ibuprofen (200 mg x 4) DRUG

Dose of 200 mg given in 6 hour intervals the first 24 hours postoperatively

Treatment D:

Placebo (x4) DRUG

Given in 6 hour intervals the first 24 hours postoperatively

Treatment B:; Treatment C:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Scheduled for unilateral, primary Total Hip Arthroplasty (THA)
• Age \> 18
• ASA 1-3.
• BMI \> 18 and \< 40
• Women in the fertile age must have negative urine HCG pregnancy test
• Patients who gave their written informed consent to participating in the trial after having fully understood the contents of the protocol and restrictions.

You may not qualify if:

• Patients who cannot cooperate with the trial.
• Concomitant participation in another trial
• Patients who cannot understand or speak Danish.
• Daily use of strong opioids (tramadol and codein are accepted)
• Patients with allergy to the medicines used in the trial.
• Contraindications against NSAID, for example previous ulcer, heart failure, liver failure, or renal failure (eGRF \< 60 ml/kg/1,73m2), known thrombocytopenia (\<100 mia/L)
• Patients suffering from alcohol and/or drug abuse - based on the investigator's judgement.

Sponsors & Collaborators

• Daniel Hägi-Pedersen: lead
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator

Study Sites (6)

Gildhøj Privathospital

Copenhagen, Brøndby, 2605, Denmark

Location

Holbæk Hospital

Holbæk, 4300, Denmark

Location

Køge Hospital

Køge, 4600, Denmark

Location

Nykøbing Falster Hospital

Nykøbing Falster, 4800, Denmark

Location

Næstved Hospital

Næstved, 4700, Denmark

Location

Odense University Hospital (OUH)

Odense, 5000, Denmark

Location

Related Publications (3)

• Thybo KH, Hagi-Pedersen D, Wetterslev J, Dahl JB, Schroder HM, Bulow HH, Bjorck JG, Mathiesen O. PANSAID - PAracetamol and NSAID in combination: study protocol for a randomised trial. Trials. 2017 Jan 10;18(1):11. doi: 10.1186/s13063-016-1749-7.

  PMID: 28069072 BACKGROUND

• Thybo KH, Hagi-Pedersen D, Dahl JB, Wetterslev J, Nersesjan M, Jakobsen JC, Pedersen NA, Overgaard S, Schroder HM, Schmidt H, Bjorck JG, Skovmand K, Frederiksen R, Buus-Nielsen M, Sorensen CV, Kruuse LS, Lindholm P, Mathiesen O. Effect of Combination of Paracetamol (Acetaminophen) and Ibuprofen vs Either Alone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty: The PANSAID Randomized Clinical Trial. JAMA. 2019 Feb 12;321(6):562-571. doi: 10.1001/jama.2018.22039.

  PMID: 30747964 DERIVED

• Thybo KH, Jakobsen JC, Hagi-Pedersen D, Pedersen NA, Dahl JB, Schroder HM, Bulow HH, Bjorck JG, Overgaard S, Mathiesen O, Wetterslev J. PANSAID-PAracetamol and NSAID in combination: detailed statistical analysis plan for a randomised, blinded, parallel, four-group multicentre clinical trial. Trials. 2017 Oct 10;18(1):465. doi: 10.1186/s13063-017-2203-1.

  PMID: 29017585 DERIVED

Related Links

• Trial Website

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Acetaminophen; Ibuprofen

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Daniel Hägi-Pedersen, MD, PhD

  Department of Anaesthesiology, Næstved Hospital

  STUDY CHAIR

• Kasper H Thybo, MD

  Department of Anaesthesiology, Næstved Hospital

  PRINCIPAL INVESTIGATOR

• Ole Mathiesen, MD, PhD

  Department of Anaesthesiology, Køge Hospital

  STUDY CHAIR

• Jørgen B Dahl, MD, DMSc

  Department of Anaesthesiology, Bispebjerg Hospital

  STUDY CHAIR

• Jørn Wetterslev, MD, PhD

  Copenhagen Trial Unit, Center for Clinical Intervention Research

  STUDY CHAIR

• Martin Pohlman, MD

  Department of Anaesthesiology, Nykøbing Falster Hospital

  STUDY CHAIR

• Hans Henrik Bülow, MD

  Department of Anaesthesiology, Holbæk Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant

Study Record Dates

• First Submitted: October 7, 2015
• First Posted: October 8, 2015
• Study Start: November 1, 2015
• Primary Completion: October 1, 2017
• Study Completion: January 1, 2018
• Last Updated: February 12, 2018

Record last verified: 2018-02

Locations

DK (6)