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

24 de agosto de 2017 actualizado por: 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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Actual)

53

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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 de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Triple

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: 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.
Droga: FE 202158 1.25
FE 202158 at dose 1.25 ng/kg/min infused.
Experimental: 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.
Droga: FE 202158 2.5
FE 202158 at dose 2.5 ng/kg/min infused.
Experimental: 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.
Droga: FE 202158 3.75
FE 202158 at dose 3.75 ng/kg/min infused.
Comparador de placebos: PLCBO
Patients in the arm received an intravenous infusion for up to 7 days of placebo.
Otro: Placebo
Isotonic saline infused.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)
Periodo de tiempo: 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
Periodo de tiempo: 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.
Periodo de tiempo: 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.
Periodo de tiempo: 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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Ferring Pharmaceuticals

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de noviembre de 2009

Finalización primaria (Actual)

1 de agosto de 2011

Finalización del estudio (Actual)

1 de septiembre de 2011

Fechas de registro del estudio

Enviado por primera vez

30 de septiembre de 2009

Primero enviado que cumplió con los criterios de control de calidad

22 de octubre de 2009

Publicado por primera vez (Estimar)

23 de octubre de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

25 de septiembre de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

24 de agosto de 2017

Última verificación

1 de agosto de 2017

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

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

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

Ensayos clínicos sobre Shock séptico

Ensayos clínicos sobre FE 202158 1.25

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