Investigating FE 202158 as Potential Primary Treatment in Patients With Early Septic Shock

Study Overview
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Brief Summary
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The purpose of this trial is to investigate the potential of FE 202158 as a treatment which can stabilize blood pressure for treatment of patients in early septic shock.

Official Title
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An Open Label Feasibility Trial Investigating FE 202158 as Potential Primary Vasopressor Treatment in Patients With Vasodilatory Hypotension in Early Septic Shock.

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: FE 202158


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form by the patient or a legal representative according to local regulations' Man or women 18 years of age or older Body weight below 115 kg for male patients and 100 kg for female patients Proven or suspected infection Septic shock, i.e. vasodilatory hypotension requiring vasopressor support Willing to use an adequate barrier method or hormonal method of contraception, if not abstinent, from informed consent to one week after the end of infusion of study medication Exclusion Criteria: Present or a history within the last 6 months of symptoms of acute coronary syndrome (myocardial infarction or unstable angina) Known or suspected endocarditis Hypovolaemia suspected on clinical grounds, e.g. cold extremities with delayed capillary filling, low cardiac filling pressure, marked systolic or pulse pressure variation or positive leg raising test Known or suspected cardiac failure Known or suspected infection with (HIV)-1, HIV-2, hepatitis B, or hepatitis C Pregnancy or breastfeeding Any cause of hypotension other than early septic shock Use of vasopressin or terlipressin within 7 days prior to start of IMP infusion Proven or suspected acute mesenteric ischemia, as judged by the investigator Known episode of septic shock within 1 month prior to screening Death anticipated within 24 hours, or due to the underlying disease within 3 months Known past or current 2nd and 3rd degree AV-block without a well functioning pacemaker Brain injury within current hospitalisation Present hospitalisation with burn injury Symptomatic peripheral vascular disease including Raynaud's syndrome Previously included in this trial Intake of an Investigational Medicinal Product (IMP) within the last 3 months (or longer if judged by the Investigator to possibly influence the outcome of the current study) Known participation in another interventional clinical trial Considered by the investigator to be unsuitable to participate in the trial for any other reason

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug<br>FE 202158 | Drug: FE 202158<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Mean arterial pressure (MAP) was measured intra-arterially on a continuous basis. Success percentage of patients maintaining target/adequate MAP (>60 mmHg) without norepinephrine is presented. | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | 
| Cumulative Dose of FE 202158 | Cumulative dose of FE 202158 was calculated from Day 1 up to Day 7. | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | 
| Infusion Rate of FE 202158 | Infusion rate of FE 202158 was presented from Day 1 up to Day 7. | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | 
| Cumulative Dose of Norepinephrine | Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Cumulative dose of norepinephrine was calculated from Day 1 up to Day 7. | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | 
| Infusion Rate of Norepinephrine | Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Infusion rates and all changes in infusion rates of norepinephrine were recorded continuously during the 7 day maximum treatment period. | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | 
| Time to Septic Shock Resolution | The Kaplan-Meyer estimation of time to out of septic shock was estimated where time to (first) septic shock resolution was defined as time of end of infusion regimen. Intermittent off treatment periods were regarded as part of the shock duration. Time to all but one patient out of septic shock is presented. | Day 1 up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Output | The urinary output was recorded every 24 hours up to Day 7, or as long as the patient was in intensive care unit. | Day 1 up to Day 7 post-infusion (Data collected on Day 1 at 24 h, Day 2 at 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | 
| Fluid Balance | The fluid balance (accumulated input/output) was recorded in 24-hour collecting periods when the patient was in the intensive care unit and during the infusion of FE 202158. | Day 1 up to Day 7 post-infusion (Data collected on Day 1 at 24 h, Day 2 at 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | 
| Summary of Investigator Reported Outcomes | Investigator reported outcome on FE 202158 performance. Answers were graded on a visual analogue scale (VAS) from 0 to 10, 0 being the worst and 10 being the best outcome. | Day 1 up to Day 2 | 
| Morbidity Assessment | Percentage of all the Days alive and out/free of intensive care unit, hospital, dialysis, or ventilation within Day 28 were summarized. Patients dying before or at Day 28 were counted as zero. | Day 1 up to Day 28 | 
| Graded Morbidity | Collection of data on graded morbidity was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital. | Day 1 up to Day 28 | 
| Mortality | Collection of data on mortality was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital. | Day 1 up to Day 28 | 
| Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Significant changes for vital signs (blood pressure, heart rate, mean arterial pressure), electrocardiogram (ECG), and laboratory parameters (clinical chemistry, haematology, haemostasis, and urinary parameters). | Day 1 up to Day 7, and at follow-up assessments performed 24-72 hours after end of IMP infusion |