Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock
- Conditions
- Shock, Septic
- Interventions
- Registration Number
- NCT04055909
- Lead Sponsor
- Inotrem
- Brief Summary
This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.
- Detailed Description
All patients with a diagnosis of septic shock will be considered for study participation. All potential study patients will receive standard of care for the treatment of septic shock.
After screening for eligibility, patients meeting all inclusion and no exclusion criterion will be randomized. Patients will be randomized to one of three treatment arms.
Treatment with study drug must be initiated as early as possible, but no later than 24 hours after the onset of septic shock, defined by the start of vasopressor therapy.
Patients will be treated for at least 3 days with study drug. After the first 3 days of treatment, patients still requiring vasopressor will be treated until 24 hours after vasopressor withdrawal with a maximum treatment duration of 5 days.
Patients will be assessed at the End of Study (EoS) visit at day 28. After the last patient's day 28 visit, the study will be analyzed. Additional follow up (FU) visits will be conducted after 90 days, 6 and 12 months.
The objective of the study ist to compare the safety, tolerability and efficacy of two doses of nangibotide versus placebo, when given in addition to standard of care.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 355
- Provide written informed consent
- Age 18 to 85 years (inclusive)
- Documented or suspected infection: lung, abdominal or urinary tract infection (UTI) in the elderly (≥65 years)
- Organ dysfunction defined as acute change in total SOFA score ≥ 2 points
- Refractory hypotension requiring vasopressors to maintain MAP ≥65mm Hg despite adequate volume resuscitation
- Hyperlactatemia (blood lactate >2 mmol/L or 18 mg/dL).
- Previous episode of septic shock requiring vasopressor administration within current hospital stay
- Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids >75 mg prednisone daily or equivalent for more than 7 days
- Immunosuppressive therapy related to recent (<6 months) transplantation
- Cancer chemotherapy (<3 months) implying an immunodepression
- Known HIV infection with low CD4 cell count (<200) for at least 6 months
- Known pregnancy (positive urine or serum pregnancy test)
- Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding
- Ongoing documented or suspected endocarditis, history of prosthetic heart valves
- Prolonged QT syndrome
- End-stage neurological disease
- End-stage cirrhosis (Child Pugh Class C)
- Acute Physiology and Chronic Health Evaluation (APACHE II) score <15 or ≥ 34
- Home oxygen therapy on a regular basis for > 6 h/day
- Recent cardiopulmonary resuscitation (CPR) (within current hospital stay)
- Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg
- Moribund patients
- Decision to limit full care taken before obtaining informed consent
- Participation in another interventional study in the 3 months prior to randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description nangibotide 2 nangibotide high dose Treatment with study drug at at dose of 1.0mg/kg/hr Placebo placebo Treatment with a matched placebo infusion nangibotide 1 nangibotide low dose Treatment with study drug at at dose of 0.3mg/kg/hr
- Primary Outcome Measures
Name Time Method Sequential organ failure assessment (SOFA) score day 5 Change of total SOFA score from baseline to day 5 (in the subgroup defined by patients with elevated sTREM-1 baseline levels and in the overall population)
- Secondary Outcome Measures
Name Time Method Sepsis support index (SSI) day 28 Sepsis support index
Duration of Invasive mechanical ventilation (IMV) day 28 Change in the Duration of Invasive mechanical ventilation (IMV)
Duration of Renal support day 28 Change in the Duration of renal replacement therapy, RRT
Incidence of secondary infections and post shock antibiotic use day 28 Incidence of secondary infections and post shock antibiotic use
Overall survival up to 12 months 12 months Overall survival up to 12 months
All-cause mortality 12 months all-cause mortality up to 12 months
Organe support free survival day 28 time to organe support free
Septic shock related mortality at day 28 day 28 mortality caused by septic shock
Duration of ICU stay day 28 hospitalization
Overall survival on day 28 day 28 time from the date of study drug start to date of death from any cause
Daily change of total Sequential organ failure assessment (SOFA) score and individual subscores day 1, day 2, day 3, day 4, day 5, day 6 and day 7 Daily change of total SOFA score and individual subscores
Duration of Vasopressor use day 28 Change in the Duration of Vasopressor use
Alive and organ support free at day 28 day 28 Proportion of patients alive and free of organ support at day 28
Trial Locations
- Locations (43)
Tampereen yliopistollinen sairaala
🇫🇮Tampere, Finland
UZ Gent
🇧🇪Gent, Belgium
CHU Marie Curie
🇧🇪Lodelinsart, Belgium
Helsinki University Hospital Adult ICU PPDS
🇫🇮Helsinki, Finland
Kuopion Yliopistollinen sairaala
🇫🇮Kuopio, Finland
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Ziekenhuis Oost-Limburg
🇧🇪Genk, Belgium
Clinique Saint-Pierre
🇧🇪Ottignies, Belgium
Centre hospitalier Jolimont-Lobbes
🇧🇪La Louvière, Belgium
CHU UCL Namur asbl
🇧🇪Yvoir, Belgium
Nordsjællandshospital Hillerød
🇩🇰Hillerod, Denmark
Centre hospitalier de Béthune
🇫🇷Béthune, France
Centre hospitalier Victor Dupouy
🇫🇷Argenteuil, France
CHRU Nancy - Hôpital Central
🇫🇷Nancy, France
CHU Angers
🇫🇷Angers, France
Hôpital Fleyriat
🇫🇷Bourg-en-Bresse, France
Hôpital de Bicêtre
🇫🇷Le Kremlin Bicêtre, France
CHD les Oudairies
🇫🇷La Roche sur Yon, France
CHU Dijon - Hôpital François Mitterrand
🇫🇷Dijon, France
CHRU Lille - Hôpital Roger Salengro
🇫🇷Lille, France
CHU LE Mans
🇫🇷Le Mans, France
Hôpital Universitaire Dupuytren
🇫🇷Limoges, France
Hôpital Nord
🇫🇷Marseille, France
Centre hospitalier de Melun
🇫🇷Melun, France
Centre Hospitalier Lyon Sud
🇫🇷Lyon, France
Hôpital Saint Louis
🇫🇷Paris, France
Hôtel Dieu - Nanates
🇫🇷Nantes, France
CHU de Nîmes
🇫🇷Nîmes, France
Hôpital de la source
🇫🇷Orléans, France
Hôpital Lariboisière
🇫🇷Paris, France
Hôpital d'instruction des Armées Robert Picqué
🇫🇷Villenave d'Ornon, France
Groupe hospitalier Pitié-Salpêtrière
🇫🇷Paris, France
Hôpital Cochin
🇫🇷Paris, France
CHRU Hôpital Bretonneau
🇫🇷Tours, France
St Jame's Hospital
🇮🇪Dublin, Ireland
Galway University Hospital
🇮🇪Galway, Ireland
Hospital Universitario Vall d'Hebrón
🇪🇸Barcelona, Spain
Hospital del mar
🇪🇸Barcelone, Spain
Hospital Clinical San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Dentral de Asturias
🇪🇸Oviedo, Spain
Hospital Universitari Mutua de Terrassa
🇪🇸Terrassa, Spain
Hospital universitario DR. Peset Aleixandre
🇪🇸Valencia, Spain
Hospital Universitario y Politecnico la Fe
🇪🇸Valencia, Spain