E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with intermediate severity pulmonary embolism |
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E.1.1.1 | Medical condition in easily understood language |
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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 | LLT |
E.1.2 | Classification code | 10014521 |
E.1.2 | Term | Embolism pulmonary |
E.1.2 | System Organ Class | 100000004855 |
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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 |
To demonstrate the clinical benefits of tenecteplase over placebo in normotensive patients with acute pulmonary embolism and right ventricular dysfunction.
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E.2.2 | Secondary objectives of the trial |
To assess the safety after administration of tenecteplase in normotensive patients with acute pulmonary embolism and with echocardiographic (or spiral CT) and laboratory evidence of right ventricular dysfunction. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- age 18 years or older;
- acute PE (first symptoms occurring 15 days or less before randomisation)
- right ventricular dysfunction confirmed by echocardiography or spiral computed tomography of the chest and a positive troponin I or T test.
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E.4 | Principal exclusion criteria |
- Haemodynamic collapse
- Known significant bleeding risk
- Administration of thrombolytic agents within the previous 4 days
- Uncontrolled hypertension defined as systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg at randomisation
- Pregnancy, lactation or parturition within the previous 30 days. Women of childbearing age must have a negative pregnancy test or use a medically accepted method of birth control
- Known coagulation disorder (including vitamin K antagonists and platelet count <100 000/mm3)
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E.5 End points |
E.5.1 | Primary end point(s) |
- Primary efficacy endpoint is all-cause mortality or haemodynamic collapse within 7 days.
- Secondary efficacy endpoints are: death, haemodynamic collapse, confirmed symptomatic pulmonary embolism recurrence within 7 days and all cases of death within 30 days
- Safety criteria for this study are: total strokes (intracranial hemorrhage or ischemic stroke) within 7 days, major bleeding (excluding ICH) within 7 days and any serious adverse events within 30 days.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Death within 7 days
• Haemodynamic collapse within 7 days
• Confirmed symptomatic pulmonary embolism recurrence within 7 days
• Death within 30 days
• Total strokes (intra cranial haemorrhage or ischaemic stroke) within 7 days
• Major bleeding (other than ICH) within 7 days defined as
– Moderate bleed: requires blood transfusion(s) but which is not deemed life-threatening and does not lead to haemodynamic compromise requiring emergency fluid replacement, inotropic support, or interventional treatment
– Severe bleed: leads to haemodynamic compromise requiring:
• Requiring emergency intervention (such as replacement of fluid and/or blood products, inotropic support, or surgical treatment)
• life-threatening
• fatal
• Serious adverse events within 30 days
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | 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) | No |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 88 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Mexico |
Poland |
Portugal |
Romania |
Serbia |
Slovenia |
Spain |
Switzerland |
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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
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Premature termination of the trial may happen under the following conditions: occurrence of unknown or increase of known adverse events that render the risk/benefit ratio unacceptable, interim analysis indicates reason (see section 7.3.5), an unacceptable high number of SAEs, ethical justification, recruitment rate is too low such that it is unrealistic to consider completion of the trial within an acceptable period of time, at the request of the MAH, decision of the authorities. |
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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 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |