E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postoperative pain after total knee arthroplasty |
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E.1.1.1 | Medical condition in easily understood language |
Postoperative pain after total knee arthroplasty |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023469 |
E.1.2 | Term | Knee arthroplasty |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054711 |
E.1.2 | Term | Postoperative pain |
E.1.2 | System Organ Class | 100000004863 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this trial is to investigate the analgesic efficacy and safety of one or two doses of dexamethasone after total knee arthroplasty |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
One-year follow-up with EQ-5D-5L, Oxford-Knee-Score and mortality including need for medical attention. Analysis of high and low pain responders. Troponin (TnI) levels 24 and 48 hours postoperatively (only at Naestved Hospital). Establishment of a bio-bank (blood-samples) for future studies (only at Naestved Hospital). |
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E.3 | Principal inclusion criteria |
• Scheduled for unilateral, primary TKA, not Oxford (“uni-knee”). • Age ≥ 18 • ASA 1-3 • BMI ≥ 18.0 and ≤ 40.0 • Negative urine HCG pregnancy test and use of anti-conception for women in the fertile age • Patients who gave their written informed consent to participating in the trial after having fully understood the contents of the protocol and restrictions
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E.4 | Principal 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 at daily use of systemic glucocorticoids • 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 bil/l); or against treatment with glucocorticoids. • Dysregulated diabetes (investigators judgement) • Patients suffering from alcohol and/or drug abuse – based on the investigator's judgement
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E.5 End points |
E.5.1 | Primary end point(s) |
Total need for i.v.-equivalent morphine for the first 48 hours postoperatively administered as patient controlled analgesia (PCA) morphine (0-24 hours), on demand oral morphine (24-48 hours) and supplemental morphine administered at the post-anaesthesia unit the first hour postoperatively after end of surgery (general anaesthesia) or end of spinal anaesthesia. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
i.v.-equivalent morphine for the first 48 hours postoperatively |
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E.5.2 | Secondary end point(s) |
• Total need of i.v. morphine the first 24 hours postoperatively • Total need of oral morphine the following 24-48 hours • VAS-pain scores (visual analogue scale (VAS)): o at rest at 6, 24 and 48 hours postoperatively. o with active 45 degrees flexion of the knee (VAS) at 6, 24 and 48 hours postoperatively o highest and average score during the first 24 hours and 24-48 hours • Timed up and go (TUG) test at 24 and 48 hours including maximum pain during the TUG test. • Adverse events o Level of nausea at 6, 24 and 48 hours postoperatively o Level of sedation at 6, 24 and 48 hours postoperatively o Level of dizziness at 6, 24 and 48 hours postoperatively o Number of vomiting episodes (0-48 hours) measured in the periods 0-24 and 24-48 hours postoperatively o Number of patients with one or more patient-reported adverse events in the intervention period • Consumption of ondansetron (and DHB) in the period 0-24 and 24-48 hours postoperatively • Quality of sleep 0-24 and 24-48 hours postoperatively • Level of fatigue at 24 and 48 hours postoperatively • Questionnaire on pain, sleep, satisfaction and use of medication for postoperative days 3-7 • Number of patients with one or more serious adverse events (SAE), including death, within 90 days after surgery defined as SAE (according to ICH-GCP-guidelines), except “prolongation of hospitalisation” • 90 days follow-up conducted by telephone with qualitative participant reported assessments using EQ5D5L + Oxford-Knee-Score and also need for medical attention and/or intervention including need for anti-biotics and/or re-operation
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See E.5.2 for timepoints in relation to the specific endpoint |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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90 days after the last subject's surgery |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |