Shock, SepticPhase 2ASTONISHNCT04055909
Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock
A Phase 2 study testing nangibotide low dose and nangibotide high dose in people with Shock, Septic, run by Inotrem at 43 sites in 6 countries.
Trial summary
This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Shock, Septic
- What is being tested?
- nangibotide low dose and nangibotide high dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 355 participants
- Where
- 43 sitesin 6 countries
- Study dates
- 13 Nov 2019to 9 May 2023
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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)
Show all 18Show fewer
- 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
Trial locations and contacts
43 sites in 6 countries.
43 sites in 6 countries
France23 sites
CHU Angers
Angers, 49933
Centre hospitalier Victor Dupouy
Argenteuil, 95100
Centre hospitalier de Béthune
Béthune, 62408
Hôpital Fleyriat
Bourg-en-Bresse, 01000
CHU Dijon - Hôpital François Mitterrand
Dijon, 21079
CHD les Oudairies
La Roche-sur-Yon, 85925
Hôpital de Bicêtre
Le Kremlin-Bicêtre, 94270
CHU LE Mans
Le Mans, 72000
CHRU Lille - Hôpital Roger Salengro
Lille, 59037
Hôpital Universitaire Dupuytren
Limoges
Centre Hospitalier Lyon Sud
Lyon, 69495
Hôpital Nord
Marseille, 13015
Centre hospitalier de Melun
Melun, 77000
CHRU Nancy - Hôpital Central
Nancy, 54035
Hôtel Dieu - Nanates
Nantes, 44093
CHU de Nîmes
Nîmes, 30029
Hôpital de la source
Orléans, 45067
Hôpital Lariboisière
Paris, 75010
Hôpital Saint Louis
Paris, 75010
Groupe hospitalier Pitié-Salpêtrière
Paris, 75013
Hôpital Cochin
Paris, 75014
CHRU Hôpital Bretonneau
Tours, 37044
Hôpital d'instruction des Armées Robert Picqué
Villenave-d'Ornon, 33882
Belgium7 sites
Cliniques Universitaires Saint-Luc
Brussels
Ziekenhuis Oost-Limburg
Genk, 3600
UZ Gent
Ghent, 9000
Centre hospitalier Jolimont-Lobbes
La Louvière, 7100
CHU Marie Curie
Lodelinsart, 6042
Clinique Saint-Pierre
Ottignies, 1340
CHU UCL Namur asbl
Yvoir, 5530
Spain7 sites
Hospital del mar
Barcelona, 08003
Hospital Universitario Vall d'Hebrón
Barcelona
Hospital Clinical San Carlos
Madrid, 28040
Hospital Universitario Dentral de Asturias
Oviedo, 33011
Hospital Universitari Mutua de Terrassa
Terrassa, 08221
Hospital universitario DR. Peset Aleixandre
Valencia, 46017
Hospital Universitario y Politecnico la Fe
Valencia, 46026
Finland3 sites
Helsinki University Hospital Adult ICU PPDS
Helsinki, PL 340
Kuopion Yliopistollinen sairaala
Kuopio, PO BOX 1777
Tampereen yliopistollinen sairaala
Tampere, PL 2000
Ireland2 sites
St Jame's Hospital
Dublin
Galway University Hospital
Galway, H91 YR71
About this study
Official title: Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study
This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.
Read the 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.
- Conditions
- Shock, Septic
- Being tested
- nangibotide low dose, nangibotide high dose, placebo
- Keywords
- Septic Shock
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nangibotide low doseDrug
Also called LR12
nangibotide 0.3 mg/kg/h
nangibotide high doseDrug
Also called LR12
nangibotide 1.0 mg/kg/h
placeboDrug
Also called matched placebo
matching placebo
| Study group | Role | What they receive |
|---|---|---|
| nangibotide 1 | Experimental | Treatment with study drug at at dose of 0.3mg/kg/hr Receives: Drug: nangibotide low dose |
| nangibotide 2 | Experimental | Treatment with study drug at at dose of 1.0mg/kg/hr Receives: Drug: nangibotide high dose |
| Placebo | Placebo comparator | Treatment with a matched placebo infusion Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: day 5
Secondary outcomes (14)
All-cause mortality
all-cause mortality on D5 and D28
Measured: day 5 and day 28
Duration of ICU stay
hospitalization
Measured: day 28
Organe support free survival
time to organe support free
Measured: day 28
Sepsis support index (SSI)
Sepsis support index
Measured: day 28
Daily change of total Sequential organ failure assessment (SOFA) score and individual subscores
Daily change of total SOFA score and individual subscores
Measured: day 1, day 2, day 3, day 4, day 5, day 6 and day 7
Duration of Vasopressor use
Change in the Duration of Vasopressor use
Measured: day 28
Duration of Invasive mechanical ventilation (IMV)
Change in the Duration of Invasive mechanical ventilation (IMV)
Measured: day 28
Duration of Renal support
Change in the Duration of renal replacement therapy, RRT
Measured: day 28
All-cause mortality
all-cause mortality up to 12 months
Measured: 12 months
Septic shock related mortality at day 28
mortality caused by septic shock
Measured: day 28
Incidence of secondary infections and post shock antibiotic use
Incidence of secondary infections and post shock antibiotic use
Measured: day 28
Alive and organ support free at day 28
Proportion of patients alive and free of organ support at day 28
Measured: day 28
Overall survival on day 28
time from the date of study drug start to date of death from any cause
Measured: day 28
Overall survival up to 12 months
Overall survival up to 12 months
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2019
- Study start13 Nov 2019
- Primary completion9 May 2022
- Study completion9 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Shock, SepticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 355 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inotrem
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jean-Jacques Garaud, MD, Study director, CEO and Medical Officer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04055909
- Sponsor's protocol ID
- MOT-C-203
- Other IDs
- 2018-004827-36, 2018
- Acronym
- ASTONISH
- Status last verified
- Apr 2023
- First submitted
- 12 Aug 2019
- Last updated
- 11 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Francois B, Lambden S, Fivez T, Gibot S, Derive M, Grouin JM, Salcedo-Magguilli M, Lemarie J, De Schryver N, Jalkanen V, Hicheur T, Garaud JJ, Cuvier V, Ferrer R, Bestle M, Pettila V, Mira JP, Bouisse C, Mercier E, Vermassen J, Huberlant V, Vinatier I, Anguel N, Levy M, Laterre PF; ASTONISH investigators. Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial. Lancet Respir Med. 2023 Oct;11(10):894-904. doi: 10.1016/S2213-2600(23)00158-3. Epub 2023 May 31.
PubMed 37269870Francois B, Lambden S, Gibot S, Derive M, Olivier A, Cuvier V, Witte S, Grouin JM, Garaud JJ, Salcedo-Magguilli M, Levy M, Laterre PF. Rationale and protocol for the efficacy, safety and tolerability of nangibotide in patients with septic shock (ASTONISH) phase IIb randomised controlled trial. BMJ Open. 2021 Jul 7;11(7):e042921. doi: 10.1136/bmjopen-2020-042921.
PubMed 34233965
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study
- ClinicalTrials.gov ID
- NCT04055909
- Acronym / sponsor ID
- ASTONISH / MOT-C-203
- Conditions
- Shock, Septic
- Keywords
- Septic Shock
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 355 participants (actual)
- Lead sponsor
- InotremIndustry (pharma, biotech, devices)
- Study start
- 13 Nov 2019 (actual)
- Primary completion
- 9 May 2022 (actual)
- Study completion
- 9 May 2023 (estimated)
- First posted
- 14 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| nangibotide 1 | Experimental | Drug: nangibotide low doseTreatment with study drug at at dose of 0.3mg/kg/hr |
| nangibotide 2 | Experimental | Drug: nangibotide high doseTreatment with study drug at at dose of 1.0mg/kg/hr |
| Placebo | Placebo comparator | Drug: placeboTreatment with a matched placebo infusion |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nangibotide low doseAlso: LR12nangibotide 0.3 mg/kg/h | Drug | nangibotide 1 |
| nangibotide high doseAlso: LR12nangibotide 1.0 mg/kg/h | Drug | nangibotide 2 |
| placeboAlso: matched placebomatching placebo | Drug | Placebo |
Primary outcome
Sequential organ failure assessment (SOFA) score
Time frame: 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)
14 secondary outcomes
All-cause mortality
Time frame: day 5 and day 28
Duration of ICU stay
Time frame: day 28
Organe support free survival
Time frame: day 28
Sepsis support index (SSI)
Time frame: day 28
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
Duration of Vasopressor use
Time frame: day 28
Duration of Invasive mechanical ventilation (IMV)
Time frame: day 28
Duration of Renal support
Time frame: day 28
All-cause mortality
Time frame: 12 months
Septic shock related mortality at day 28
Time frame: day 28
Incidence of secondary infections and post shock antibiotic use
Time frame: day 28
Alive and organ support free at day 28
Time frame: day 28
Overall survival on day 28
Time frame: day 28
Overall survival up to 12 months
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2023.
- Derived from this study: PubMed 37269870Francois B, Lambden S, Fivez T, Gibot S, Derive M, Grouin JM, Salcedo-Magguilli M, Lemarie J, De Schryver N, Jalkanen V, Hicheur T, Garaud JJ, Cuvier V, Ferrer R, Bestle M, Pettila V, Mira JP, Bouisse C, Mercier E, Vermassen J, Huberlant V, Vinatier I, Anguel N, Levy M, Laterre PF; ASTONISH investigators. Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial. Lancet Respir Med. 2023 Oct;11(10):894-904. doi: 10.1016/S2213-2600(23)00158-3. Epub 2023 May 31.
- Derived from this study: PubMed 34233965Francois B, Lambden S, Gibot S, Derive M, Olivier A, Cuvier V, Witte S, Grouin JM, Garaud JJ, Salcedo-Magguilli M, Levy M, Laterre PF. Rationale and protocol for the efficacy, safety and tolerability of nangibotide in patients with septic shock (ASTONISH) phase IIb randomised controlled trial. BMJ Open. 2021 Jul 7;11(7):e042921. doi: 10.1136/bmjopen-2020-042921.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Jacques Garaud, MD study director
CEO and Medical Officer
43 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nangibotide low dose and nangibotide high dose in people with Shock, Septic, run by Inotrem at 43 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in France, Belgium, Spain, Finland, Ireland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sequential organ failure assessment (SOFA) score (time frame: day 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04055909, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2023.