E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic thoracic pain after cardiac surgery via sternotomy |
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E.1.1.1 | Medical condition in easily understood language |
chronic thoracic pain (pain on chest) after cardiac surgery |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine the influence of intra-operative use of remifentanil versus fentanyl on the percentage of patients with chronic pain one year after cardiac surgery. |
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E.2.2 | Secondary objectives of the trial |
-percentage of patients with chronic thoracic pain and their mean NRS scores three months and six months after cardiac surgery. - effect on the quality of life (QoL) and on the use of analgesics three months, six months and one year after surgery - pain thresholds will be measured, evaluating the difference in postoperative pain threshold (three days and one year after surgery) compared to preoperative pain threshold (baseline), using quantitative sensory testing. - other aspects in the postoperative period, e.g. NRS scores, postoperative consumption of analgesics, length of ICU- and hospital stay, safety parameters of remifentanil - influence of genetic variances involved in pain sensitivity (e.g. GCH-1, WDF-4, ZNF, MC1R) and in pharmacokinetics and pharmacodynamics of opiates (e.g. UGT, MRP, OPRM1, COMT) will be investigated. - cost-effectiveness analysis alongside the RCT with a 12 month follow-up will be performed.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients living in Utrecht and surroundings undergoing cardiac surgery via sternotomy, including a CABG and/or valve replacement, admitted to the ICU or PACU in the St. Antonius hospital, between 18 and 85 years old, weighing between 45 and 140 kg, written informed consent. |
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E.4 | Principal exclusion criteria |
- Pregnancy/ breastfeeding - Language barrier - History of drug abuse - Neurologic condition such as peripheral neuropathy - Known morphine or paracetamol allergy - BMI > 35 kg/m2
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of patients reporting chronic thoracic pain one year after cardiac surgery. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
one year after cardiac surgery |
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E.5.2 | Secondary end point(s) |
- The percentage of patients reporting chronic thoracic pain three months and six months after cardiac surgery - The mean NRS score of patients with chronic thoracic pain three months and six months after cardiac surgery. - The quality of life (QoL) three months, six months and one year after surgery. - The difference in postoperative pain thresholds three days and one year after cardiac surgery compared to the preoperative pain threshold (baseline) - The use of analgesics three months, six months and one year after cardiac surgery. - The percentage of patients with at least one NRS-score of ≥ 4 at rest during ICU and hospital stay - The mean NRS per patient at rest during ICU stay - The required amounts of analgesics (morphine/paracetamol) during hospital stay - Length of ICU and hospital stay - Total administered amount of remifentanil and fentanyl - Total medical costs during one year, including costs of hospitalization days (ICU and non-ICU) and costs of medications - Productivity costs during one year (i.e., foregone paid and unpaid work and reduced productivity while at work) - Cost-effectiveness, expressed as incremental costs per case of chronic pain at 12 months after cardiac surgery avoided and incremental costs per quality-adjusted life-year (QALY) gained - Safety parameters of remifentanil; such as nausea, constipation, respiratory depression, duration of ventilation, hallucinations, delirium, Glascow Coma Scale, renal function) - Genetic variances involved in pain sensitivity (e.g. GCH-1, WDF-4, ZNF, MC1R) and pharmacokinetics and pharmacodynamics of opiates (e.g. UGT, MRP, OPRM1, COMT)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
peri- and postoperative period, 3 months, 6 months and 1 year after cardiac surgery |
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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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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End of the trial is approximately one year after the last patient's visit for cardiac 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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |