- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04055909
Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock (ASTONISH)
Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Bruxelles, Belgium
- Cliniques Universitaires Saint-Luc
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Genk, Belgium, 3600
- Ziekenhuis Oost-Limburg
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Gent, Belgium, 9000
- UZ Gent
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La Louvière, Belgium, 7100
- Centre Hospitalier Jolimont-Lobbes
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Lodelinsart, Belgium, 6042
- CHU Marie Curie
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Ottignies, Belgium, 1340
- Clinique Saint-Pierre
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Yvoir, Belgium, 5530
- CHU UCL Namur asbl
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Hillerod, Denmark, DK-3400
- Nordsjællandshospital Hillerød
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Helsinki, Finland, PL 340
- Helsinki University Hospital Adult ICU PPDS
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Kuopio, Finland, PO BOX 1777
- Kuopion Yliopistollinen Sairaala
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Tampere, Finland, PL 2000
- Tampereen yliopistollinen sairaala
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Angers, France, 49933
- CHU Angers
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Argenteuil, France, 95100
- Centre Hospitalier Victor Dupouy
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Bourg-en-Bresse, France, 01000
- Hôpital Fleyriat
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Béthune, France, 62408
- Centre Hospitalier de Béthune
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Dijon, France, 21079
- Chu Dijon - Hôpital François Mitterrand
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La Roche sur Yon, France, 85925
- CHD Les Oudairies
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Le Kremlin Bicêtre, France, 94270
- Hopital de Bicetre
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Le Mans, France, 72000
- CHU Le Mans
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Lille, France, 59037
- CHRU Lille - Hôpital Roger Salengro
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Limoges, France
- Hôpital Universitaire Dupuytren
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Lyon, France, 69495
- Centre Hospitalier Lyon Sud
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Marseille, France, 13015
- Hopital Nord
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Melun, France, 77000
- Centre Hospitalier de Melun
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Nancy, France, 54035
- CHRU Nancy - Hôpital central
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Nantes, France, 44093
- Hôtel Dieu - Nanates
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Nîmes, France, 30029
- CHU de Nîmes
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Orléans, France, 45067
- Hôpital de la Source
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Paris, France, 75010
- Hôpital Saint Louis
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Paris, France, 75010
- Hopital Lariboisiere
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Paris, France, 75014
- Hôpital Cochin
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Paris, France, 75013
- Groupe Hospitalier Pitie-Salpetriere
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Tours, France, 37044
- CHRU Hôpital Bretonneau
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Villenave d'Ornon, France, 33882
- Hôpital d'Instruction des Armées Robert Picqué
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Dublin, Ireland
- St Jame's Hospital
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Galway, Ireland, H91 YR71
- Galway University Hospital
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Barcelona, Spain
- Hospital Universitario Vall d'Hebron
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Barcelone, Spain, 08003
- Hospital del Mar
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Madrid, Spain, 28040
- Hospital Clinical San Carlos
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Oviedo, Spain, 33011
- Hospital Universitario Dentral de Asturias
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Terrassa, Spain, 08221
- Hospital Universitari Mútua de Terrassa
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Valencia, Spain, 46026
- Hospital Universitario y Politécnico La Fe
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Valencia, Spain, 46017
- Hospital Universitario Dr. Peset Aleixandre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: nangibotide 1
Treatment with study drug at at dose of 0.3mg/kg/hr
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nangibotide 0.3 mg/kg/h
Other Names:
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Experimental: nangibotide 2
Treatment with study drug at at dose of 1.0mg/kg/hr
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nangibotide 1.0 mg/kg/h
Other Names:
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Placebo Comparator: Placebo
Treatment with a matched placebo infusion
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matching placebo
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sequential organ failure assessment (SOFA) score
Time Frame: day 5
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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)
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day 5
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
All-cause mortality
Time Frame: day 5 and day 28
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all-cause mortality on D5 and D28
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day 5 and day 28
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Duration of ICU stay
Time Frame: day 28
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hospitalization
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day 28
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Organe support free survival
Time Frame: day 28
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time to organe support free
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day 28
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Sepsis support index (SSI)
Time Frame: day 28
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Sepsis support index
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day 28
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Daily change of total Sequential organ failure assessment (SOFA) score and individual subscores
Time Frame: day 1, day 2, day 3, day 4, day 5, day 6 and day 7
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Daily change of total SOFA score and individual subscores
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day 1, day 2, day 3, day 4, day 5, day 6 and day 7
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Duration of Vasopressor use
Time Frame: day 28
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Change in the Duration of Vasopressor use
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day 28
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Duration of Invasive mechanical ventilation (IMV)
Time Frame: day 28
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Change in the Duration of Invasive mechanical ventilation (IMV)
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day 28
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Duration of Renal support
Time Frame: day 28
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Change in the Duration of renal replacement therapy, RRT
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day 28
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All-cause mortality
Time Frame: 12 months
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all-cause mortality up to 12 months
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12 months
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Septic shock related mortality at day 28
Time Frame: day 28
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mortality caused by septic shock
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day 28
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Incidence of secondary infections and post shock antibiotic use
Time Frame: day 28
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Incidence of secondary infections and post shock antibiotic use
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day 28
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Alive and organ support free at day 28
Time Frame: day 28
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Proportion of patients alive and free of organ support at day 28
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day 28
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Overall survival on day 28
Time Frame: day 28
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time from the date of study drug start to date of death from any cause
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day 28
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Overall survival up to 12 months
Time Frame: 12 months
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Overall survival up to 12 months
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12 months
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Jean-Jacques Garaud, MD, CEO and Medical Officer
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MOT-C-203
- 2018-004827-36 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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