| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 |
| To assess the effect of reversal of neuromuscular blockade with sugammadex 4 mg.kg-1 compared with reversal according to usual care (neostigmine or spontaneous reversal) on the incidence of adjudicated post-surgical events of bleeding over 24 hours, in patients receiving thromboprophylaxis and undergoing hip fracture surgery or joint (hip/knee) replacement with neuromuscular blockade induced by rocuronium or vecuronium. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the effect of reversal of neuromuscular blockade with sugammadex 4 mg.kg-1 compared with reversal according to usual care (neostigmine or spontaneous reversal) on activated partial thromboplastin time (aPTT) (with values over a period of up to 2 hours in a subset of patients).
To assess the safety of reversal of neuromuscular blockade with sugammadex 4 mg.kg-1 compared with reversal according to usual care (neostigmine or spontaneous reversal).
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Each patient must be willing and able to provide written informed consent for the trial.
2. Each patient must be ≥18 years of age. A patient may be of either sex, any race/ethnicity.
3. Each patient must be ASA (American Society of Anesthesiologists) Class 1 or 2 or 3.
4. Each patient must be scheduled for a surgical procedure of hip fracture surgery or joint (hip or knee) replacement surgery under general anesthesia including the use of rocuronium or vecuronium for neuromuscular blockade with/without endotracheal intubation and with accessibility for blood draws as specified for the duration of the planned procedure.
5. At screening, patients must be:
a. Currently receiving ongoing thromboprophylactic therapy with LMWH or UFH;
or
b. Planned to initiate thromboprophylactic therapy with LMWH or UFH prior to or during surgery (ie, prior to administration of study medication);
or
c. Currently receiving thromboprophylactic therapy with a vitamin K antagonist (or other thromboprophylactic agent) which has been temporarily substituted with peri-operative LMWH or UFH;
and/or
d. Currently receiving ongoing thromboprophylaxis with low-dose aspirin or other antiplatelet therapy (eg, clopidogrel, ticlopidine, dipyridamole); Ongoing therapy is defined as therapy which has not been discontinued in anticipation of surgery; brief, temporary (ie, less than 2 days prior to surgery) interruption of antiplatelet therapy, such as for the purposes of preoperative fasting, does not constitute discontinuation of therapy.
6. Locally-obtained platelet count screening value (and central laboratory value, if results already received by investigator) must be above the lower limit of normal range.
7. Must be an appropriate candidate for rapid reversal of neuromuscular blockade (eg, planned extubation in operating room).
8. Each patient must be able to adhere to visit schedules.
9. Each sexually active female patient of child-bearing potential must agree to use a medically accepted method of contraception through seven days after receiving protocol-specified medication. Medically accepted methods of contraception include condoms (male or female) with a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), inert or copper-containing IUD, surgical sterilization (eg, hysterectomy or tubal ligation). Further, for patients using hormonal contraceptives, if study medication is administered on the same day an oral contraceptive is taken, the patient must follow the missed dose advice in the package leaflet of the oral contraceptive. In the case of non-oral hormonal contraceptives, the patient must use an additional non-hormonal contraceptive method and refer to the advice in the package leaflet of the product. Postmenopausal women are not required to use contraception. Postmenopausal is defined as at least 12 consecutive months without a spontaneous menstrual period.
10. To participate in the pharmacogenetic analysis, the patient must be willing to give written informed consent for the pharmacogenetic testing and able to adhere to dose and visit schedules.
Note: A patient unwilling to sign the informed consent for pharmacogenetic testing may be included in the trial; however, pharmacogenetic samples must not be obtained.
|
|
| E.4 | Principal exclusion criteria |
1. Has or is suspected to have anatomical malformations that may lead to difficult intubation.
2. Has or is suspected to have a neuromuscular disorder that may affect neuromuscular blockade.
3. Has or is suspected to have a medical history that includes a coagulation disorder, bleeding diathesis, systemic lupus erythematosus or antiphospholipid syndrome.
4. Has a history or evidence of active abnormal bleeding or blood clotting (eg, thrombosis) within the 30 days prior to screening.
5. Has or is suspected to have significant hepatic dysfunction that would prevent participation in the trial as determined by the Investigator.
6. Has or is suspected to have severe renal insufficiency (eg, estimated creatinine clearance of < 30 mL/minute).
7. Has or is suspected to have a (family) history of malignant hyperthermia.
8. Has or is suspected to have a hypersensitivity or hypersensitivity-like reaction to sugammadex, muscle relaxants or their excipients, or other medication(s) used during general anesthesia.
9. Is planned to be administered toremifene and/or fusidic acid via intravenous administration within 24 hours before or within 24 hours after study medication administration.
10. Has experienced recent, severe trauma that would prevent participation in the trial as determined by the Investigator.
11. Is morbidly obese (Body Mass Index > 35).
12. Has or is suspected to have any condition that would contraindicate the administration of sugammadex (for all patients screened) or neostigmine/ glycopyrrolate (or neostigmine/atropine at sites using atropine) (for patients planned for Usual Care Group 1).
13. Is a premenopausal female of childbearing potential who is pregnant or intends to become pregnant between randomization and the Day 30 pregnancy follow-up visit.
14. Is a female patient who is breast-feeding.
15. Is known to have been previously treated with sugammadex or has participated in a sugammadex clinical trial.
16. Has participated in any other clinical trial within the 30 days (inclusive) prior to signing the informed consent form for this current trial.
17. Has direct involvement with this current study and is employed by or is a family member of an individual employed by the Investigator, the investigational site, or the Sponsor.
18.Has an active hip/knee infection and is scheduled for revision surgery. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| suspected, unanticipated post-surgical events of bleeding that are subsequently confirmed by adjudication |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 24 hours after administration |
|
| E.5.2 | Secondary end point(s) |
| coagulation endpoints: aPTT, PT(INR) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| after study medication (10 and 60 min after study medication, also at 3, 20, 30,120 minutes post study medication in subset for pK sampling), unscheduled visit |
|
| 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 | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| 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) | 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 | 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| 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
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| 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
|
| Each patient is considered to have ended participation in the trial when he/she has completed the last protocol-specified contact (eg, visits or telephone contacts) or prematurely discontinues from the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
