A study to find the appropriate dose of S62798 to treat patients with pulmonary circulation blocked by a clot

Phase 1

• Conditions: Acute intermediate high risk pulmonary embolism (PE); MedDRA version: 21.0Level: PTClassification code 10037377Term: Pulmonary embolismSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2019-003514-14-GR
• Lead Sponsor: Institut de Recherches Internationales Servier

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-03-24
• Last Update Posted: 7 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 370

Inclusion Criteria

1. Acute pulmonary embolism and categorized as intermediate-high risk and documented by CT pulmonary angiography (CTPA), V/Q scan, V/Q SPECT or pulmonary angiography with emboli in at least one segmental or more proximal artery
2. Troponin I or high sensitivity Troponin T elevated as per local lab
3. Evidence of right ventricular dysfunction (RVD) on echocardiography or CTPA
4. With at least one of the following clinical criteria:
o SBP lower than 110 mmHg for > 15 min or,
o Respiratory rate > 20 per min or SaO2 < 90% on room air or,
o Sinus tachycardia = 110 bpm sustained over 30 seconds.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 185
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 185

Exclusion Criteria

1. Presence of right heart thrombus
2. Reperfusion therapy planned.
3. Patients with forbidden previous or concomitant treatment
4. Known or pre-existing chronic pulmonary hypertension
5. Uncontrolled hypertension defined as SBP>180 mm Hg and/or DBP >110 mm Hg
6. Patients with a high risk of haemorrhage
7. Patients with less than 3 months of life expectancy
8. Platelet count lower than 100 G/L (100 000 platelets/µL), INR above 1.5 or abnormal aPTT not explained by concomitant anticoagulation therapy
9. Positive results of pregnancy test or lacting women

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the dose-response relationship of S62798 on the RV/LV end-diastolic diameter (EDD) 24h after treatment initiation, in patients with intermediate-high risk pulmonary embolism (PE) on heparin.;Secondary Objective: ­To assess the effect of S62798 on secondary efficacy endpoints such as TAPSE, and PE-related clinical events.<br>­To assess the safety profile of S62798 in the study population.<br>­To assess the pharmacokinetics of S62798 (and metabolites if applicable).;Primary end point(s): Right /left ventricular end-diastolic diameter (RV/LV EDD)<br><br>;Timepoint(s) of evaluation of this end point: 24h (±2h) after treatment initiation

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. RV/LV EDD <br>2. Tricuspid annular plane systolic excursion (TAPSE) estimated by echocardiography <br>3. Adjudicated PE-related clinical events<br>4. Pharmacokinetic measurements ;Timepoint(s) of evaluation of this end point: 1. For RV/LV EDD: 48h (±4h) and 30d (±2d)<br>2. For tricuspid annular plane systolic excursion (TAPSE) estimated by echocardiography: 24h (±2h), 48h (±4h) and 30d (±2d)<br>3. For adjudicated PE-related clinical events: Between baseline and day 30<br>4. For pharmacokinetic measurements: Between baseline and day 6