E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myocardial injury (as measured by plasma troponin) after major surgery. |
|
E.1.1.1 | Medical condition in easily understood language |
Myocardial injury after major surgery. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 | 10061024 |
E.1.2 | Term | Cardiac disorder |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 | 10061024 |
E.1.2 | Term | Cardiac disorder |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 |
To determine whether continuing ACE-I and/or ARB treatment perioperatively reduces the risk of perioperative myocardial injury in patients undergoing major surgery. This assessment will be based on plasma troponin levels measured in the first 48 hours postoperatively. |
|
E.2.2 | Secondary objectives of the trial |
Secondary Objectives: To determine whether ACE-I and/or ARB cessation is linked to more episodes of clinically relevant hypotension, heart rate changes and infectious morbidity. |
|
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 |
Mechanistic substudies to run in parallel exploring: 1. Changes in autonomic function [measured using Holter monitors recording heart rate] 2. Immune function- assessed from serial blood samples. |
|
E.3 | Principal inclusion criteria |
• Informed consent (no incapacitated or vulnerable adult or minors will be included). • Age 60 years and over. • Undergoing major surgery (major joint replacement/ vascular/ gastrointestinal) requiring general and/or regional anaesthesia with sedation. • Currently taking ACE-I, ARB or combined ACE-I and ARB therapy. • Duration of surgery longer than 120 minutes. • ASA grade 3 or above. • All female subjects must be postmenopausal, as demonstrated by clinical history or demonstrated not to be pregnant though a preoperative pregnancy test. |
|
E.4 | Principal exclusion criteria |
• Current participation in any other trials where care or treatment is being altered. • Recent myocardial infarction (within 3 months). • Any condition, which in the opinion of the treating clinician would result in the patient being harmed by the cessation of the ACE-I and/or ARB therapy. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome measure: To determine whether continuing ACE-I and/or ARB perioperatively reduces the risk of perioperative myocardial injury. Primary Endpoint: high-sensitivity plasma troponin levels, a sensitive marker of perioperative myocardial injury, in first 48h postoperatively. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
24h and 48h after surgery. |
|
E.5.2 | Secondary end point(s) |
Secondary endpoint: To determine whether ACE-I and/or ARB cessation is linked to increased episodes of clinically relevant hypotension, heart rate changes and infectious morbidity.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
postoperative morbidity for the entire duration of hospital stay. |
|
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 | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Primary outcome blinded to patients/clinicians |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Cessation versus continuation of patients usual drug |
|
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
| 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 | 5 |
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 | Yes |
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
|
Last visit of the last subject undergoing the trial. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 30 |