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Trial record 1 of 1 for:    02571361
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PAracetamol and NSAID in Combination: A Randomised, Blinded, Parallel, 4-group Clinical Trial (PANSAID)

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ClinicalTrials.gov Identifier: NCT02571361
Recruitment Status : Completed
First Posted : October 8, 2015
Last Update Posted : February 12, 2018
Sponsor:
Collaborator:
Copenhagen Trial Unit, Center for Clinical Intervention Research
Information provided by (Responsible Party):
Daniel Hägi-Pedersen, Naestved Hospital

Tracking Information
First Submitted Date  ICMJE October 7, 2015
First Posted Date  ICMJE October 8, 2015
Last Update Posted Date February 12, 2018
Study Start Date  ICMJE November 2015
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 15, 2016)
  • Morphine consumption the first 24 hours postoperatively [ Time Frame: 0-24 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
  • Serious adverse events [ Time Frame: 0-90 days postoperatively ]
    Serious adverse events, including death, within 90 days after surgery defined as SAE (according to ICH-GCP-guidelines) except "prolongation of hospitalisation"
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2015)
  • Morphine comsumption the first 24 hours postoperatively [ Time Frame: 0-24 hours postoperatively ]
    Total need for morphine administered as patient controlled analgesia (PCA) for the first 24 hours postoperatively. Bolus 2.0 mg; lockout: 10 min
  • Serious adverse events [ Time Frame: 0-90 days postoperatively ]
    Serious adverse events, including death, within 90 days after surgery defined as SAE (according to ICH-GCP-guidelines) except "prolongation of hospitalisation"
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2015)
  • Pain during movement at 6 hours postoperatively (visual analogue scale) [ Time Frame: 6 hours postoperatively ]
    Pain scores (visual analogue scale (VAS)) with active 30 degrees flexion of the hip at 6 hours postoperatively. No pain = 0; worst imaginable pain = 100
  • Pain during movement at 24 hours postoperatively (visual analogue scale) [ Time Frame: 24 hours postoperatively ]
    Pain scores (visual analogue scale (VAS)) with active 30 degrees flexion of the hip at 24 hours postoperatively. No pain = 0; worst imaginable pain = 100
  • Pain at rest at 6 hours postoperatively (visual analogue scale) [ Time Frame: 6 hours postoperatively ]
    Pain scores (visual analogue scale (VAS)) at rest at 6 hours postoperatively. No pain = 0; worst imaginable pain = 100
  • Pain at rest at 24 hours postoperatively (visual analogue scale) [ Time Frame: 24 hours postoperatively ]
    Pain scores (visual analogue scale (VAS)) at rest at 24 hours postoperatively. No pain = 0; worst imaginable pain = 100
  • Adverse events [ Time Frame: 0-24 hours postoperatively ]
    Number of patients with one or more adverse events in the intervention period (0-24 hours)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 20, 2016)
  • Nausea at 6 hours postoperatively (Verbal rating scale) [ Time Frame: 6 hours postoperatively ]
    Level of nausea at 6 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
  • Nausea at 24 hours postoperatively (Verbal rating scale) [ Time Frame: 24 hours postoperatively ]
    Level of nausea at 24 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
  • Vomiting the first 24 hours postoperatively [ Time Frame: 0-24 hours postoperatively ]
    Number of vomiting episodes (0-24 hours) measured in the periods 0-6 and 6-24 hours postoperatively
  • Anti-emetic treatment the first 24 hours postoperatively [ Time Frame: 0-24 hours postoperatively ]
    Consumption of ondansetron in the period 0-24 hours postoperatively
  • Sedation at 6 hours postoperatively (Verbal rating scale) [ Time Frame: 6 hours postoperatively ]
    Level of sedation at 6 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
  • Sedation at 24 hours postoperatively (Verbal rating scale) [ Time Frame: 24 hours postoperatively ]
    Level of sedation at 24 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
  • Blood loss intraoperatively [ Time Frame: intraoperatively ]
    Blood loss during the surgical procedure (intraoperatively)
  • Days alive and outside hospital within 90 days after surgery. [ Time Frame: 0-90 days postoperatively ]
    Days alive and outside hospital within 90 days after surgery.
  • Dizziness at 6 hours postoperatively (Verbal rating scale) [ Time Frame: 6 hours postoperatively ]
    Level of dizziness at 6 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
  • Dizziness at 24 hours postoperatively (Verbal rating scale) [ Time Frame: 24 hours postoperatively ]
    Level of dizziness at 24 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
Original Other Pre-specified Outcome Measures
 (submitted: October 7, 2015)
  • Nausea at 6 hours postoperatively (Verbal rating scale) [ Time Frame: 6 hours postoperatively ]
    Degree of nausea at 6 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
  • Nausea at 24 hours postoperatively (Verbal rating scale) [ Time Frame: 24 hours postoperatively ]
    Degree of nausea at 24 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
  • Vomiting the first 24 hours postoperatively [ Time Frame: 0-24 hours postoperatively ]
    Number of vomiting episodes (0-24 hours) measured in the periods 0-6 and 6-24 hours postoperatively
  • Anti-emetic treatment the first 24 hours postoperatively [ Time Frame: 0-24 hours postoperatively ]
    Consumption of ondansetron in the period 0-24 hours postoperatively
  • Sedation at 6 hours postoperatively (Verbal rating scale) [ Time Frame: 6 hours postoperatively ]
    Degree of sedation at 6 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
  • Sedation at 24 hours postoperatively (Verbal rating scale) [ Time Frame: 24 hours postoperatively ]
    Degree of sedation at 24 hours postoperatively. Verbal rating scale: none, mild, moderate or severe
  • Blood loss intraoperatively [ Time Frame: intraoperatively ]
    Blood loss during the surgical procedure (intraoperatively)
  • Days alive and outside hospital within 90 days after surgery. [ Time Frame: 0-90 days postoperatively ]
    Days alive and outside hospital within 90 days after surgery.
 
Descriptive Information
Brief Title  ICMJE PAracetamol and NSAID in Combination: A Randomised, Blinded, Parallel, 4-group Clinical Trial
Official Title  ICMJE PAracetamol and NSAID in Combination: A Randomised, Blinded, Parallel, 4-group Clinical Trial
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.

Detailed Description

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.

Sub-studies: We preplan the following sub-studies. :

  1. A subgroup analysis of benefit outcomes (pain and opioid consumption) with respect to the following sub-groups: sex, age (below vs above 65 years old), ASA-score (I+II vs III), Use of analgesic medication before surgery (none vs any) and anaesthetic technique (general anaesthesia vs. spinal anaesthesia). Please find a detailed protocol at www.pansaid.dk
  2. A subgroup analysis of harm (serious adverse events and adverse events) with respect to the following groups sex, age (below vs above 65 years old), use of NSAIDs before surgery, and ASA-score (I+II vs III). Please find a detailed protocol at www.pansaid.dk
  3. Longer follow-up than the specified 90 days (1 year)
  4. An analysis of the association between VAS-scores and opioid consumption
  5. Time-to-event analyses regarding use of PCA-morphine
  6. An analysis of the association between preoperative analgesic use and pain/morphine consumption
  7. An analysis of the individual patients: how many will achieve "no worse than mild pain" (NRS<3). Please find a detailed protocol at www.pansaid.dk

More sub-studies may be performed post-hoc and they will be clearly identified as such.

Oversight of amendments and approvals Protocol version 2: Approved 12 August 2015: First approved version of the trial protocol

Protocol version 3: Approved 21 January 2016: Clarification of what happens in case of an SAE and definition of major protocol violations

Protocol version 4: Approved 15 June 2016: Clarification of the primary outcome, clarification that steroids are not permitted in the intervention period, and addition of an exploratory outcome (dizziness)

Protocol version 5: Approved 21 December 2016: Clarification of the exclusion criteria of contraindication to paracetamol and addition of stub-studies

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pain, Postoperative
Intervention  ICMJE
  • Drug: Paracetamol (1g x 4)
    Dose of 1 g given in 6 hour intervals the first 24 hours postoperatively
    Other Name: Acetaminophen
  • Drug: Ibuprofen (400 mg x 4)
    Dose of 400 mg given in 6 hour intervals the first 24 hours postoperatively
  • Drug: Paracetamol (0,5 g x 4)
    Dose of 0,5 g given in 6 hour intervals the first 24 hours postoperatively
    Other Name: Acetaminophen
  • Drug: Ibuprofen (200 mg x 4)
    Dose of 200 mg given in 6 hour intervals the first 24 hours postoperatively
  • Drug: Placebo (x4)
    Given in 6 hour intervals the first 24 hours postoperatively
Study Arms  ICMJE
  • Active Comparator: Treatment A:
    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.
    Interventions:
    • Drug: Paracetamol (1g x 4)
    • Drug: Ibuprofen (400 mg x 4)
  • Active Comparator: Treatment B:
    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.
    Interventions:
    • Drug: Paracetamol (1g x 4)
    • Drug: Placebo (x4)
  • Active Comparator: Treatment C:
    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.
    Interventions:
    • Drug: Ibuprofen (400 mg x 4)
    • Drug: Placebo (x4)
  • Active Comparator: Treatment D:
    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.
    Interventions:
    • Drug: Paracetamol (0,5 g x 4)
    • Drug: Ibuprofen (200 mg x 4)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 7, 2015)
556
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2018
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02571361
Other Study ID Numbers  ICMJE SM2-KHT-2015 - v2
2015-002239-16 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Daniel Hägi-Pedersen, Naestved Hospital
Study Sponsor  ICMJE Daniel Hägi-Pedersen
Collaborators  ICMJE Copenhagen Trial Unit, Center for Clinical Intervention Research
Investigators  ICMJE
Study Chair: Daniel Hägi-Pedersen, MD, PhD Department of Anaesthesiology, Næstved Hospital
Principal Investigator: Kasper H Thybo, MD Department of Anaesthesiology, Næstved Hospital
Study Chair: 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
PRS Account Naestved Hospital
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP