- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01000649
Effects of the V1a Agonist FE 202158 in Patients With Septic Shock
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
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Brussels, Belgio
- Clinique Universitaire St-Luc
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Brussels, Belgio
- Erasme Hospital (Free University of Brussels)
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Brussels, Belgio
- University Hospital Vrije Universiteit
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Dinant, Belgio
- Service des Soins Intensits
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Vancouver, Canada
- Royal Columbian Hospital
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Vancouver, Canada
- St. Paul´s Hospital
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Bispebjerg, Danimarca
- Bispebjerg Hospital
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Copenhagen, Danimarca
- Rigshospitalet
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Hillerød, Danimarca
- Hillerød Hospital
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Hvidovre, Danimarca
- Hvidovre Hospital
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Delaware
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Newark, Delaware, Stati Uniti
- Christiana Care Health System
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Massachusetts
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Springfield, Massachusetts, Stati Uniti
- Baystate Medical Center
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Minnesota
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Duluth, Minnesota, Stati Uniti
- Division of Education and Research SMDC Health System
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New Jersey
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Camden, New Jersey, Stati Uniti
- Cooper University Hospital
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New York
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New York, New York, Stati Uniti
- Mount Sinai School of Medicine
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Texas
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Houston, Texas, Stati Uniti
- Baylor College of Medicine
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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. |
FE 202158 at dose 1.25 ng/kg/min infused.
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Sperimentale: 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. |
FE 202158 at dose 2.5 ng/kg/min infused.
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Sperimentale: 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. |
FE 202158 at dose 3.75 ng/kg/min infused.
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Comparatore placebo: PLCBO
Patients in the arm received an intravenous infusion for up to 7 days of placebo.
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Isotonic saline infused.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)
Lasso di tempo: Day 1 up to Day 7
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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
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Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE
Lasso di tempo: Day 1 up to Day 7
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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
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Cumulative Dose of Open Label NE.
Lasso di tempo: Day 1 up to Day 7
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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
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Infusion Rates of Open Label NE.
Lasso di tempo: Day 1 up to Day 7
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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
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration
Lasso di tempo: Day 1 up to Day 7
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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
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PK Parameter in Patients : Time to Steady State
Lasso di tempo: Day 1 up to Day 7
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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
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PK Parameter in Patients : Clearance
Lasso di tempo: Day 1 up to Day 7
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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
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PK Parameter in Patients : Steady State Volume of Distribution
Lasso di tempo: Day 1 up to Day 7
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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
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PK Parameter in Patients : Initial Elimination Half-life
Lasso di tempo: Day 1 up to Day 7
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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
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PK Parameter in Patients : Terminal Elimination Half-life
Lasso di tempo: Day 1 up to Day 7
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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
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Change From Baseline in C-reactive Protein (CRP)
Lasso di tempo: Day 1 up to Day 7
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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
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Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha
Lasso di tempo: At Day 1, Day 2, Day 4, and Day 7
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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
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Change From Baseline in Interleukin-6 (IL-6)
Lasso di tempo: At Day 1, Day 2, Day 4, and Day 7
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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
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Change From Baseline in Interleukin-10 (IL-10)
Lasso di tempo: At Day 1, Day 2, Day 4, and Day 7
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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
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Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist
Lasso di tempo: At Day 1, Day 2, Day 4, and Day 7
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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
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Change From Baseline in Heart Rate
Lasso di tempo: Day 1 up to Day 7
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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
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Change From Baseline in Fluid Balance
Lasso di tempo: Day 1 up to Day 7
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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
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SOFA Score
Lasso di tempo: Day 1 up to Day 7, Day 14 and Day 29
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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
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Pulmonary Function : Change From Baseline in PaO2/FiO2
Lasso di tempo: Day 1 up to Day 7
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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
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Pulmonary Function : Change From Baseline in Tidal Volume
Lasso di tempo: Day 1 up to Day 7
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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
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Change From Baseline in Arterial Blood Gas (Lactate)
Lasso di tempo: Day 1 up to Day 7
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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
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Days Alive and Free of Any Organ Dysfunction at Day 7
Lasso di tempo: At Day 7
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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
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Percentage of Patients Alive and Free of All Vasopressors
Lasso di tempo: At Day 7, Day 14 and Day 28
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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
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Percentage of Days Alive and Free of Dialysis
Lasso di tempo: At Day 7, Day 14 and Day 28
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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
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Percentage of Days Alive and Free of Ventilation
Lasso di tempo: At Day 7
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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
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Mortality
Lasso di tempo: At Day 1, 7, 14, and 28
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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
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Incidence of Abnormal Changes in ECG
Lasso di tempo: Day 1 up to Day 7
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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
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Collaboratori e investigatori
Sponsor
Pubblicazioni e link utili
Pubblicazioni generali
- Russell JA, Vincent JL, Kjolbye AL, Olsson H, Blemings A, Spapen H, Carl P, Laterre PF, Grundemar L. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients. Crit Care. 2017 Aug 15;21(1):213. doi: 10.1186/s13054-017-1798-7.
- Rehberg S, Yamamoto Y, Sousse L, Bartha E, Jonkam C, Hasselbach AK, Traber LD, Cox RA, Westphal M, Enkhbaatar P, Traber DL. Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis. Am J Physiol Heart Circ Physiol. 2012 Nov 15;303(10):H1245-54. doi: 10.1152/ajpheart.00390.2012. Epub 2012 Sep 7.
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- FE 202158 CS02
- EudraCT: 2009-010798-19
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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Assistance Publique - Hôpitaux de ParisTraumabase Group; Capgemini Invent; Ecole polytechnique; EHESS (Ecole des hautes... e altri collaboratoriReclutamentoFerite e lesioni | Shock emorragico | Shock traumaticoFrancia
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King's College Hospital NHS TrustUniversity Hospital BirminghamCompletatoShock emorragico traumaticoRegno Unito
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Haukeland University HospitalMinistry of Defence, NorwayCompletatoShock emorragico | Shock ipovolemicoNorvegia
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Massachusetts General HospitalBeth Israel Deaconess Medical Center; Boston Medical Center; Tufts Medical Center; Lahey Clinic e altri collaboratoriReclutamento
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Jason SperryNational Heart, Lung, and Blood Institute (NHLBI)TerminatoShock emorragicoStati Uniti
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University of Texas Southwestern Medical CenterUniversity of Washington; Resuscitation Outcomes ConsortiumCompletato
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Arsenal Medical, Inc.Non ancora reclutamentoTrauma | Shock emorragico | Emorragia dissanguante | Shock; TraumaticoStati Uniti
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Ramathibodi HospitalSconosciutoShock settico | Shock refrattarioTailandia
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German Center for Neurodegenerative Diseases (DZNE)University Hospital, BonnSconosciutoSepsi grave con shock settico | Sepsi grave senza shock setticoGermania
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Assiut UniversitySconosciuto
Prove cliniche su FE 202158 1.25
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Changchun Intellicrown Pharmaceutical Co. LTDReclutamentoSteatoepatite non alcolica (NASH)Cina
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GlyPharma TherapeuticsVectivBio AGRitiratoLinfoma, non Hodgkin, adulto | Linfoma, Hodgkin, adulto
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Swiss Federal Institute of TechnologyUnited States Agency for International Development (USAID); Quadram Institute... e altri collaboratoriCompletatoCarenza di ferro | Anemia da carenza di ferro | Carenza di ferro (senza anemia)Perù
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Ferring PharmaceuticalsCompletatoCancro alla prostataRegno Unito
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University of PennsylvaniaAttivo, non reclutanteNeoplasia mammaria | Cancro al seno metastatico | Cancro al seno positivo al recettore degli estrogeniStati Uniti
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Ferring PharmaceuticalsCompletatoIperfagia nella sindrome di Prader-WilliStati Uniti
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Kessler FoundationSconosciuto
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Swiss Federal Institute of TechnologyUniversity of MalawiCompletatoCarenza di ferro | Anemia da carenza di ferroMalawi, Svizzera
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Concordia University, MontrealCanadian Institutes of Health Research (CIHR)ReclutamentoInvecchiamento | Perdita dell'udito legata all'etàCanada
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Ferring PharmaceuticalsCompletatoIntegrazione dell'ormone lutealeGiappone