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
Overview
- Phase
- Phase 2
- Intervention
- selepressin
- Conditions
- Septic Shock
- Sponsor
- Ferring Pharmaceuticals
- Enrollment
- 868
- Locations
- 21
- Primary Endpoint
- Vasopressor- and Mechanical Ventilator-free Days (PVFDs)
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
Investigators
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
Arms & Interventions
Selepressin 3
Starting dose 3.5 ng/kg/min
Intervention: selepressin
Placebo
Intervention: placebo
Selepressin 1
Starting dose 1.7 ng/kg/min
Intervention: selepressin
Selepressin 2
Starting dose 2.5 ng/kg/min
Intervention: selepressin
Selepressin 4
Starting dose 5.0 ng/kg/min The highest dosing regimen of selepressin was not investigated in the trial as the desired primary outcome for selepressin 3 arm was not achieved, and the trial was terminated for futility.
Intervention: selepressin
Outcomes
Primary Outcomes
Vasopressor- and Mechanical Ventilator-free Days (PVFDs)
Time Frame: Up to Day 30
Composite endpoint defined as number of days from start of treatment to 30 days thereafter during which subject is: 1. Alive. However, if patient dies within these 30-days then PVFDs will be zero even if there is a period during which subject is alive and free of both vasopressor treatment and mechanical ventilation; 2. Free of treatment with vasopressors: Less than 60 min during any contiguous 24-h period. If a patient requires vasopressors longer than 60 min in total during any 24-h period, the intervening intervals during which they are free of vasopressors will not be included in the determination of PVFDs; 3. Free of any mechanical ventilation: Less than 60 min during any contiguous 24-h period. If a patient requires mechanical ventilation longer than 60 min in total during any 24-h period, the intervening intervals during which they are not receiving mechanical ventilation will not be included in the period free of mechanical ventilation in the determination of PVFDs.
Secondary Outcomes
- Duration of Mechanical Ventilation up to Day 30(Up to Day 30)
- 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)(Up to Day 30)
- Duration of RRT up to Day 90 (Excluding Subjects on RRT for Chronic Failure at the Time of Randomization)(Up to Day 90)
- Daily Urine Output Until ICU Discharge (for a Maximum of 7 Days)(Baseline and Days 1-7)
- Renal Replacement Therapy (RRT)-Free Days(Up to Day 30)
- Vasopressor-free Days up to Day 30(Up to Day 30)
- Mechanical Ventilator-free Days up to Day 30(Up to Day 30)
- 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(Days 1, 3, and 7 or discharge from ICU)
- Percentage of Subjects With New Organ Dysfunction and New Organ Failure (Based on the SOFA Score) up to Day 7 and Day 30(Up to Day 7 and Day 30)
- Cumulative Fluid Balance Until ICU Discharge (for a Maximum of 7 Days)(Baseline and Days 1-7)
- Cumulative Urine Output Until ICU Discharge (for a Maximum of 7 Days)(Baseline and Days 1-7)
- All-cause Mortality(At Day 90)
- Intensive Care Unit (ICU)-Free Days(Up to Day 30)
- Duration of Septic Shock (i.e. Vasopressor Use) up to Day 30(Up to Day 30)
- ICU Length of Stay up to Day 30(Up to Day 30)
- All-cause Mortality (Defined as the Percentage of Subjects That Have Died, Regardless of Cause) at Day 30 and Day 180(At Day 30 and Day 180)
- Daily Fluid Balance Until ICU Discharge (for a Maximum of 7 Days)(Baseline and Days 1-7)
- Utility, Based on the EuroQol Group's 5-dimension 5-level (EQ-5D-5L) Questionnaire, up to Day 180(Days 30, 60, 90 and 180)