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

24. august 2017 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

53

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Tredobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Medicin: FE 202158 1.25
FE 202158 at dose 1.25 ng/kg/min infused.
Eksperimentel: 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.
Medicin: FE 202158 2.5
FE 202158 at dose 2.5 ng/kg/min infused.
Eksperimentel: 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.
Medicin: FE 202158 3.75
FE 202158 at dose 3.75 ng/kg/min infused.
Placebo komparator: PLCBO
Patients in the arm received an intravenous infusion for up to 7 days of placebo.
Andet: Placebo
Isotonic saline infused.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)
Tidsramme: 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
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Ferring Pharmaceuticals

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. november 2009

Primær færdiggørelse (Faktiske)

1. august 2011

Studieafslutning (Faktiske)

1. september 2011

Datoer for studieregistrering

Først indsendt

30. september 2009

Først indsendt, der opfyldte QC-kriterier

22. oktober 2009

Først opslået (Skøn)

23. oktober 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

25. september 2017

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

24. august 2017

Sidst verificeret

1. august 2017

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Septisk chok

Kliniske forsøg med FE 202158 1.25

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