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

Phase 2

Completed

Conditions: Septic Shock

Interventions: Drug: FE 202158

Registration Number: NCT01612676

Lead Sponsor: Ferring Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 31

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Drug	FE 202158	FE 202158

Primary Outcome Measures

Name	Time	Method
Time to Septic Shock Resolution	Day 1 up to Day 28	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.
Infusion Rate of FE 202158	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 was presented from Day 1 up to Day 7.
Cumulative Dose of Norepinephrine	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.	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.
Cumulative Dose of FE 202158	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 was calculated from Day 1 up to Day 7.
Infusion Rate of Norepinephrine	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.	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.
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine	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.	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.

Secondary Outcome Measures

Name	Time	Method
Urinary Output	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.	The urinary output was recorded every 24 hours up to Day 7, or as long as the patient was in intensive care unit.
Morbidity Assessment	Day 1 up to Day 28	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.
Summary of Investigator Reported Outcomes	Day 1 up to Day 2	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.
Mortality	Day 1 up to Day 28	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.
Fluid Balance	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.	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.
Graded Morbidity	Day 1 up to Day 28	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.
Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram	Day 1 up to Day 7, and at follow-up assessments performed 24-72 hours after end of IMP infusion	Significant changes for vital signs (blood pressure, heart rate, mean arterial pressure), electrocardiogram (ECG), and laboratory parameters (clinical chemistry, haematology, haemostasis, and urinary parameters).

Trial Locations

Locations (4): Erasme Hospital Free University of Brussels
🇧🇪
Brussels, Belgium
Saint-Luc University Hospital
🇧🇪
Brussels, Belgium
University Hospital Brussels
🇧🇪
Brussels, Belgium
Hvidovre Hospital
🇩🇰
Hvidovre, Denmark