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Effects of the V1a Agonist FE 202158 in Patients With Septic Shock

24 sierpnia 2017 zaktualizowane przez: Ferring Pharmaceuticals

Infusion Proof-of-concept Trial Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of FE 202158 in Patients With Vasodilatory Hypotension in Early Septic Shock

The purpose of this trial was to examine the safety and tolerability, pharmacokinetics of FE 202158 and to assess whether it can stabilize blood pressure and reduce vascular (blood vessel) leakage. FE 202158 had previously been tested in healthy volunteers.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

This was a multi-centre, double-blind, randomized, placebo-controlled, parallel group trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of FE 202158 (using three ascending doses) in patients with vasodilatory hypotension in early septic shock, when given as continuous infusion for up to 7 days.

The trial comprised of three treatment arms where FE 202158 was administered in 1.25 ng, 2.5 ng and 3.75 ng dose, respectively. A placebo arm was also included in the trial where patients received isotonic saline.

Efficacy of FE 202158 was determined by evaluating its ability to maintain mean arterial pressure (MAP) >60 mmHg and its modulating effect on inflammatory markers. Effects of FE 202158 on other variables like vital signs, morbidity, mortality and pulmonary function were also determined.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

53

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Belgia
      • Brussels, Belgia
        • Clinique Universitaire St-Luc
      • Brussels, Belgia
        • Erasme Hospital (Free University of Brussels)
      • Brussels, Belgia
        • University Hospital Vrije Universiteit
      • Dinant, Belgia
        • Service des Soins Intensits
  • Dania
      • Bispebjerg, Dania
        • Bispebjerg hospital
      • Copenhagen, Dania
        • Rigshospitalet
      • Hillerød, Dania
        • Hillerød Hospital
      • Hvidovre, Dania
        • Hvidovre Hospital
  • Kanada
      • Vancouver, Kanada
        • Royal Columbian Hospital
      • Vancouver, Kanada
        • St. Paul´s Hospital
  • Stany Zjednoczone
    • Delaware
      • Newark, Delaware, Stany Zjednoczone
        • Christiana Care Health System
    • Massachusetts
      • Springfield, Massachusetts, Stany Zjednoczone
        • Baystate Medical Center
    • Minnesota
      • Duluth, Minnesota, Stany Zjednoczone
        • Division of Education and Research SMDC Health System
    • New Jersey
      • Camden, New Jersey, Stany Zjednoczone
        • Cooper University Hospital
    • New York
      • New York, New York, Stany Zjednoczone
        • Mount Sinai School of Medicine
    • Texas
      • Houston, Texas, Stany Zjednoczone
        • Baylor College of Medicine

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

Inclusion Criteria:

  • Signed informed consent form by the patient or a legal representative according to local regulations
  • Man or woman 18 years of age or older
  • Proven or suspected infection
  • Low blood pressure
  • Signs of decreased circulation in the tissues
  • Willing to use an adequate barrier method or hormonal method of contraception, if not abstinent, from the day of informed consent to one week after the end of infusion of study medication.

Exclusion Criteria:

  • Present or a history (within the last 5 years) of acute coronary syndrome (myocardial infarction or unstable angina). Patients who have been asymptomatic for 6 months after coronary revascularisation are eligible.
  • 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
  • Pregnancy or breastfeeding
  • Any cause of hypotension other than early septic shock
  • Use of vasopressin or terlipressin for blood pressure support during the current hospital admission
  • Proven or suspected acute mesenteric ischemia, as judged by the investigator
  • Known episode of septic shock within 1 month prior to randomisation
  • Underlying chronic heart disease
  • Traumatic brain injury
  • Present hospitalisation with burn injury
  • Symptomatic peripheral vascular disease including Raynaud's syndrome
  • Previously randomized in this trial
  • Intake of an investigational drug 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 clinical trial
  • Considered by the investigator to be unsuitable to participate in the trial for any other reason

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Potroić

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: FE 202158 1.25

Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min.

FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
Lek: FE 202158 1.25
FE 202158 at dose 1.25 ng/kg/min infused.
Eksperymentalny: FE 202158 2.5

Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min.

FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
Lek: FE 202158 2.5
FE 202158 at dose 2.5 ng/kg/min infused.
Eksperymentalny: FE 202158 3.75

Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 3.75 ng/kg/min.

FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.
Lek: FE 202158 3.75
FE 202158 at dose 3.75 ng/kg/min infused.
Komparator placebo: PLCBO
Patients in the arm received an intravenous infusion for up to 7 days of placebo.
Inny: Placebo
Isotonic saline infused.

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)
Ramy czasowe: Day 1 up to Day 7

Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE
Ramy czasowe: Day 1 up to Day 7

Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
Cumulative Dose of Open Label NE.
Ramy czasowe: Day 1 up to Day 7

Cumulative Dose of Open Label NE over 7 days.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
Infusion Rates of Open Label NE.
Ramy czasowe: Day 1 up to Day 7

Mean open label NE infusion rate within each predefined time period.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration
Ramy czasowe: Day 1 up to Day 7

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
PK Parameter in Patients : Time to Steady State
Ramy czasowe: Day 1 up to Day 7

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
PK Parameter in Patients : Clearance
Ramy czasowe: Day 1 up to Day 7

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
PK Parameter in Patients : Steady State Volume of Distribution
Ramy czasowe: Day 1 up to Day 7

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
PK Parameter in Patients : Initial Elimination Half-life
Ramy czasowe: Day 1 up to Day 7

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
PK Parameter in Patients : Terminal Elimination Half-life
Ramy czasowe: Day 1 up to Day 7

PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
Change From Baseline in C-reactive Protein (CRP)
Ramy czasowe: Day 1 up to Day 7

The change from Baseline in CRP levels were analysed and presented as per the planned time points.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha
Ramy czasowe: At Day 1, Day 2, Day 4, and Day 7

The change from Baseline in TNF-alpha levels were analysed and presented as per the planned time points.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
At Day 1, Day 2, Day 4, and Day 7
Change From Baseline in Interleukin-6 (IL-6)
Ramy czasowe: At Day 1, Day 2, Day 4, and Day 7

The change from Baseline in IL-6 levels were analysed and presented as per the planned time points.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
At Day 1, Day 2, Day 4, and Day 7
Change From Baseline in Interleukin-10 (IL-10)
Ramy czasowe: At Day 1, Day 2, Day 4, and Day 7

The change from Baseline in IL-10 levels were analysed and presented as per the planned time points.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
At Day 1, Day 2, Day 4, and Day 7
Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist
Ramy czasowe: At Day 1, Day 2, Day 4, and Day 7

The change from Baseline in IL-1R levels were analysed and presented as per the planned time points.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
At Day 1, Day 2, Day 4, and Day 7
Change From Baseline in Heart Rate
Ramy czasowe: Day 1 up to Day 7

The change from Baseline in heart rate was analysed and presented as per the planned time points.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
Change From Baseline in Fluid Balance
Ramy czasowe: Day 1 up to Day 7

The change from Baseline in fluid balance were analysed and presented as per the planned time points. The fluid balance was adjusted for length of time interval and weight.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
SOFA Score
Ramy czasowe: Day 1 up to Day 7, Day 14 and Day 29

The SOFA score, is used to track a patient's status during the stay in an intensive care unit. This scoring system is used to determine the extent of a person's organ function or rate of failure. The scoring system comprise of scores for six different system: Respiratory System; Nervous System; Cardiovascular System; Liver; Coagulation; and Renal System. Score for each system ranges from 0-4 (0=normal, 4=worst).

Total SOFA score is a sum of the individual system score and range from 0 to 24, 0 being the better and 24 being the worst patient status.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7, Day 14 and Day 29
Pulmonary Function : Change From Baseline in PaO2/FiO2
Ramy czasowe: Day 1 up to Day 7

Change from Baseline in PaO2/FiO2 was observed at each time-point.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
Pulmonary Function : Change From Baseline in Tidal Volume
Ramy czasowe: Day 1 up to Day 7

Change from Baseline in tidal volume was observed at each time-point.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
Change From Baseline in Arterial Blood Gas (Lactate)
Ramy czasowe: Day 1 up to Day 7

Change from Baseline in arterial blood gas (lactate) was observed at each time-point.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7
Days Alive and Free of Any Organ Dysfunction at Day 7
Ramy czasowe: At Day 7

Percentage of days alive and free of any organ dysfunction (i.e. no. of days divided by 7).

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
At Day 7
Percentage of Patients Alive and Free of All Vasopressors
Ramy czasowe: At Day 7, Day 14 and Day 28

Percentage of patients alive and free of all vasopressors was assessed on Days 7, 14, and 28.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
At Day 7, Day 14 and Day 28
Percentage of Days Alive and Free of Dialysis
Ramy czasowe: At Day 7, Day 14 and Day 28

Percentage of days alive and free of dialysis was assessed on Days 7, 14, and 28.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
At Day 7, Day 14 and Day 28
Percentage of Days Alive and Free of Ventilation
Ramy czasowe: At Day 7

Percentage of days alive and free of ventilation was assessed on Days 7, 14, and 28.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
At Day 7
Mortality
Ramy czasowe: At Day 1, 7, 14, and 28

Mortality was assessed as percentage of patients dead at pre-specified time points.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
At Day 1, 7, 14, and 28
Incidence of Abnormal Changes in ECG
Ramy czasowe: Day 1 up to Day 7

The number of patients having abnormal changes in ECG variables during the trial period was presented.

The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Day 1 up to Day 7

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Ferring Pharmaceuticals

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 listopada 2009

Zakończenie podstawowe (Rzeczywisty)

1 sierpnia 2011

Ukończenie studiów (Rzeczywisty)

1 września 2011

Daty rejestracji na studia

Pierwszy przesłany

30 września 2009

Pierwszy przesłany, który spełnia kryteria kontroli jakości

22 października 2009

Pierwszy wysłany (Oszacować)

23 października 2009

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

25 września 2017

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

24 sierpnia 2017

Ostatnia weryfikacja

1 sierpnia 2017

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • FE 202158 CS02
  • EudraCT: 2009-010798-19

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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