Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock

Shock, Septic Clinical Trial

— ASTONISH  

Official title:

Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04055909
• Other study ID #: MOT-C-203
• Secondary ID: 2018-004827-36
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 13, 2019
• Est. completion date: May 9, 2023

Study information

• Verified date: April 2023
• Source: Inotrem
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 355
• Est. completion date: May 9, 2023
• Est. primary completion date: May 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Provide written informed consent

2. Age 18 to 85 years (inclusive)

3. Documented or suspected infection: lung, abdominal or urinary tract infection (UTI) in the elderly (=65 years)

4. Organ dysfunction defined as acute change in total SOFA score = 2 points

5. Refractory hypotension requiring vasopressors to maintain MAP =65mm Hg despite adequate volume resuscitation

6. Hyperlactatemia (blood lactate >2 mmol/L or 18 mg/dL).

Exclusion Criteria:

1. Previous episode of septic shock requiring vasopressor administration within current hospital stay

2. Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids >75 mg prednisone daily or equivalent for more than 7 days

3. Immunosuppressive therapy related to recent (<6 months) transplantation

4. Cancer chemotherapy (<3 months) implying an immunodepression

5. Known HIV infection with low CD4 cell count (<200) for at least 6 months

6. Known pregnancy (positive urine or serum pregnancy test)

7. Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding

8. Ongoing documented or suspected endocarditis, history of prosthetic heart valves

9. Prolonged QT syndrome

10. End-stage neurological disease

11. End-stage cirrhosis (Child Pugh Class C)

12. Acute Physiology and Chronic Health Evaluation (APACHE II) score <15 or = 34

13. Home oxygen therapy on a regular basis for > 6 h/day

14. Recent cardiopulmonary resuscitation (CPR) (within current hospital stay)

15. Body mass index (BMI) = 40 kg/m2or weight = 130 kg

16. Moribund patients

17. Decision to limit full care taken before obtaining informed consent

18. Participation in another interventional study in the 3 months prior to randomization

Related Conditions & MeSH terms

• Shock
• Shock, Septic

Intervention

Drug:
• nangibotide low dose
nangibotide 0.3 mg/kg/h
• nangibotide high dose
nangibotide 1.0 mg/kg/h
• placebo
matching placebo

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Ziekenhuis Oost-Limburg	Genk
Belgium	UZ Gent	Gent
Belgium	Centre hospitalier Jolimont-Lobbes	La Louvière
Belgium	CHU Marie Curie	Lodelinsart
Belgium	Clinique Saint-Pierre	Ottignies
Belgium	CHU UCL Namur asbl	Yvoir
Denmark	Nordsjællandshospital Hillerød	Hillerod
Finland	Helsinki University Hospital Adult ICU PPDS	Helsinki
Finland	Kuopion Yliopistollinen sairaala	Kuopio
Finland	Tampereen yliopistollinen sairaala	Tampere
France	CHU Angers	Angers
France	Centre hospitalier Victor Dupouy	Argenteuil
France	Centre hospitalier de Béthune	Béthune
France	Hôpital Fleyriat	Bourg-en-Bresse
France	CHU Dijon - Hôpital François Mitterrand	Dijon
France	CHD les Oudairies	La Roche sur Yon
France	Hôpital de Bicêtre	Le Kremlin Bicêtre
France	CHU LE Mans	Le Mans
France	CHRU Lille - Hôpital Roger Salengro	Lille
France	Hôpital Universitaire Dupuytren	Limoges
France	Centre Hospitalier Lyon Sud	Lyon
France	Hôpital Nord	Marseille
France	Centre hospitalier de Melun	Melun
France	CHRU Nancy - Hôpital Central	Nancy
France	Hôtel Dieu - Nanates	Nantes
France	CHU de Nîmes	Nîmes
France	Hôpital de la source	Orléans
France	Groupe hospitalier Pitié-Salpêtrière	Paris
France	Hôpital Cochin	Paris
France	Hôpital Lariboisière	Paris
France	Hôpital Saint Louis	Paris
France	CHRU Hôpital Bretonneau	Tours
France	Hôpital d'instruction des Armées Robert Picqué	Villenave d'Ornon
Ireland	St Jame's Hospital	Dublin
Ireland	Galway University Hospital	Galway
Spain	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

Sponsors (1)

Lead Sponsor	Collaborator
Inotrem

Countries where clinical trial is conducted

Belgium,  Denmark,  Finland,  France,  Ireland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sequential organ failure assessment (SOFA) score	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)	day 5
Secondary	All-cause mortality	all-cause mortality on D5 and D28	day 5 and day 28
Secondary	Duration of ICU stay	hospitalization	day 28
Secondary	Organe support free survival	time to organe support free	day 28
Secondary	Sepsis support index (SSI)	Sepsis support index	day 28
Secondary	Daily change of total Sequential organ failure assessment (SOFA) score and individual subscores	Daily change of total SOFA score and individual subscores	day 1, day 2, day 3, day 4, day 5, day 6 and day 7
Secondary	Duration of Vasopressor use	Change in the Duration of Vasopressor use	day 28
Secondary	Duration of Invasive mechanical ventilation (IMV)	Change in the Duration of Invasive mechanical ventilation (IMV)	day 28
Secondary	Duration of Renal support	Change in the Duration of renal replacement therapy, RRT	day 28
Secondary	All-cause mortality	all-cause mortality up to 12 months	12 months
Secondary	Septic shock related mortality at day 28	mortality caused by septic shock	day 28
Secondary	Incidence of secondary infections and post shock antibiotic use	Incidence of secondary infections and post shock antibiotic use	day 28
Secondary	Alive and organ support free at day 28	Proportion of patients alive and free of organ support at day 28	day 28
Secondary	Overall survival on day 28	time from the date of study drug start to date of death from any cause	day 28
Secondary	Overall survival up to 12 months	Overall survival up to 12 months	12 months