Clinical trial NCT02508649: Selepressin Evaluation Programme for Sepsis-Induced Shock - Adaptive Clinical Trial
Official title: A Double-blind, Randomised, Placebo-Controlled, Phase 2b/3 Adaptive Clinical Trial Investigating the Efficacy and Safety of Selepressin as Treatment for Patients With Vasopressor-dependent Septic Shock
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Septic Shock
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-07-27
Enrollment: 868
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a double-blind, randomised, placebo-controlled, two-part adaptive clinical trial. The trial is designed to investigate the efficacy and safety of multiple dosing regimens of selepressin and to confirm the efficacy and safety of one dosing regimen in treatment of adult patients with septic shock requiring vasopressor.


Eligibility criteria: Inclusion Criteria:

* 18 years of age or older
* Proven or suspected infection
* Septic shock defined as hypotension requiring vasopressor treatment despite adequate fluid resuscitation
* Informed consent obtained in accordance with local regulations

Exclusion Criteria:

* Not possible to initiate trial drug treatment within 12 hours from onset of vasopressor treatment for septic shock
* Primary cause of hypotension not due to sepsis
* Previous severe sepsis with intensive care unit admission within this hospital stay
* Known/suspected acute mesenteric ischaemia
* Suspicion of concomitant acute coronary syndrome based on clinical symptoms and/or ECG during this episode of septic shock
* Chronic mechanical ventilation for any reason OR severe chronic obstructive pulmonary disease (COPD) requiring either continuous daily oxygen use during the preceding 30 days or mechanical ventilation (for acute exacerbation of COPD) during the preceding 30 days
* Received bone marrow transplant during the preceding 6 months or chemotherapy during the preceding 30 days for lymphoma or leukemia
* Known to be pregnant
* Decision to limit full care taken before obtaining informed consent
* Use of vasopressin in the past 12 hours prior to start of trial drug treatment or use of terlipressin within 7 days prior to start of trial drug treatment
* Prior enrolment in the trial
* Prior use of an investigational medicinal product within the last month OR planned or concurrent participation in a clinical trial for any investigational drug or investigational device

Primary outcomes:
measure: Vasopressor- and Mechanical Ventilator-free Days (PVFDs)
timeFrame: Up to Day 30
Secondary outcomes:
measure: All-cause Mortality
timeFrame: At Day 90
measure: Renal Replacement Therapy (RRT)-Free Days
timeFrame: Up to Day 30
measure: Intensive Care Unit (ICU)-Free Days
timeFrame: Up to Day 30
measure: Vasopressor-free Days up to Day 30
timeFrame: Up to Day 30
measure: Mechanical Ventilator-free Days up to Day 30
timeFrame: Up to Day 30
measure: Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30
timeFrame: Up to Day 30
measure: Duration of Mechanical Ventilation up to Day 30
timeFrame: Up to Day 30
measure: The Percentage of Subjects With RRT up to Day 30 (Counting Subjects Who Died as on RRT and Excluding Subjects on RRT for Chronic Renal Failure at the Time of Randomization)
timeFrame: Up to Day 30
measure: Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization)
timeFrame: Up to Day 90
measure: Overall and Individual Organ (Cardiovascular, Respiratory, Renal, Hepatic, Coagulation) Scores Using a Modified Version of the SOFA up to Day 7 or Until ICU Discharge
timeFrame: Days 1, 3, and 7 or discharge from ICU
measure: Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30
timeFrame: Up to Day 7 and Day 30
measure: ICU Length of Stay up to Day 30
timeFrame: Up to Day 30
measure: All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180
timeFrame: At Day 30 and Day 180
measure: Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days)
timeFrame: Baseline and Days 1-7
measure: Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days)
timeFrame: Baseline and Days 1-7
measure: Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days)
timeFrame: Baseline and Days 1-7
measure: Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days)
timeFrame: Baseline and Days 1-7
measure: Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180
timeFrame: Baseline and Days 30, 60, 90 and 180
measure: Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180
timeFrame: Days 30, 60, 90 and 180
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: Memorial Hospital
state: Colorado
city: Idaho Falls
country: United States
facility: Eastern Idaho Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Evanston
country: United States
facility: Northshore University Healthsystem Research Institute
state: Illinois
city: Topeka
country: United States
facility: Stormont Vail Health Care
state: Kansas
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Paul
country: United States
facility: HealthPartners Speciality Clinics
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Columbus
country: United States
facility: Remington Davis Inc
state: Ohio
city: Toledo
country: United States
facility: St Vincent Mercy Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc (there may be other sites in this country)
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital (there may be other sites in this country)
city: Limoges
country: France
facility: Centre Hospitalier et Universitaire de Limoges (there may be other sites in this country)
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre (there may be other sites in this country)
Study officials:
affiliation: Ferring Pharmaceuticals
name: Clinical Development Support
role: STUDY_DIRECTOR
References:
citation: Laterre PF, Berry SM, Blemings A, Carlsen JE, Francois B, Graves T, Jacobsen K, Lewis RJ, Opal SM, Perner A, Pickkers P, Russell JA, Windelov NA, Yealy DM, Asfar P, Bestle MH, Muller G, Bruel C, Brule N, Decruyenaere J, Dive AM, Dugernier T, Krell K, Lefrant JY, Megarbane B, Mercier E, Mira JP, Quenot JP, Rasmussen BS, Thorsen-Meyer HC, Vander Laenen M, Vang ML, Vignon P, Vinatier I, Wichmann S, Wittebole X, Kjolbye AL, Angus DC; SEPSIS-ACT Investigators. Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock: The SEPSIS-ACT Randomized Clinical Trial. JAMA. 2019 Oct 15;322(15):1476-1485. doi: 10.1001/jama.2019.14607.
citation: Lewis RJ, Angus DC, Laterre PF, Kjolbye AL, van der Meulen E, Blemings A, Graves T, Russell JA, Carlsen JE, Jacobsen K, Yealy DM, Opal SM, Windelov NA, Francois B, Perner A, Pickkers P, Berry SM. Rationale and Design of an Adaptive Phase 2b/3 Clinical Trial of Selepressin for Adults in Septic Shock. Selepressin Evaluation Programme for Sepsis-induced Shock-Adaptive Clinical Trial. Ann Am Thorac Soc. 2018 Feb;15(2):250-257. doi: 10.1513/AnnalsATS.201708-669SD.