Efficacy and safety of adjunctive IgM-enriched immunoglobulin therapy with a personalized dose based on serum IgM-titers vs. standard dose in patients with septic shock. A multicenter, interventional, randomized, single-blinded, two arms, adaptive study design.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Di Modena

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

11 Nov 2024 → ongoing

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

BIOTEST AG

External identifiers

EU CT number

2024-518096-57-00

EudraCT number

2018-001613-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objective is to verify the hypothesis that an adjunctive therapy with IgM-enriched immunoglobulin with a personalized dose based on serum IgM-titers is more effective in reducing any-cause mortality in patients with septic shock compared to a flat dose therapy. Mortality will be measured at 28 days.

Secondary objectives 1

1. - All cause mortality at ICU discharge, hospital discharge and at day 90; - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay. Organ dysfunction is definedas a Sequential Organ Failure Assessment (SOFA) score38 ≥3 or a Multiple organ Failure (MOF) score39 ≥1 for the corresponding organ occurring after randomization, grade of dysfunction is measured with SOFA score and with MOF score daily from randomization to day 28; - ICU free hours (IFHs) at day 28, defined as the total number of hours between ICU discharge and day 28. If death occurs during the ICU stay before day 28 the ICU free hours calculation will be 0. The ICU readmission before day 28 after randomization will be considered. - Hospital free days (HFDs) at day 90, defined as the total number of days between Hospital discharge and day 90. If death occurs during the hospital stay before day 90 the hospital free days calculation will be 0. Hospital readmissions before day 90 after randomization will be considered. - Ventilation free days (VFDs) at day 28, defined as the total number of days that patient is alive and free of ventilation between randomisation and day 28 (censored at hospital discharge). Periods of assisted breathing lasting less than 24 hours for surgical procedures will not count against the ventilation free days calculation; - Vasopressors free-days (VasoFDs) at day 28. VasoFDs is defined as the total number of days that patient is alive and free of vasopressors between randomisation and day 28 (censored at hospital discharge); - Antibiotic free days (AFDs) at day 28, defined as the total number of days that the patient is alive and free of antibiotic drugs administration between randomisation and day 28 (censored at hospital discharge). - ICU acquired weakness at 7, 28 and 90 days or hospital discharge defined by Medical Research Council (MRC) Scale. - Occurrence of protocol related adverse events at day 28

Conditions and MedDRA coding

Septic shock

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Age > 18 years; 2. Septic shock occurrence < 24 hours; septic shock is identified according to Sepsis-3 definition by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia in patients with sepsis2. Sepsis is defined as a life threatening organ dysfunction identified as an acute change in total SOFA score ≥2 points consequent to the infection; 3. IgM-titers< 60mg/dl (or < 20% of the lower threshold value of local laboratory) within 24 hours from shock occurrence.

Exclusion criteria 1

1. 1. Shock of uncertain diagnosis; 2. Hypersensitivity to IgM Preparation in use or its excipients; 3. Patients receiving intravenous immunoglobulins (e.g. IgG or IgM enriched preparations) for > 6 hours before enrolment; 4. Selective absolute IgA deficiency with antibodies to IgA; 5. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available; 6. Clinical decision to withhold life-sustaining treatment or “too sick to benefit”; 7. Neutrophil count <1.000/mm3; 8. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition); 9. Patients with a known, chronic kidney dysfunction needing dialysis (creatinine ≥ 3.4 mg/dl or creatinine clearance ≤ 30 ml/min/1.73m2); 10. Body Mass Index (BMI) >40; 11. Participation in other clinical trials on adjunctive therapies for sepsis (during past 3 months); 12. Lack or withdrawal of informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. All-cause mortality at day 28.

Secondary endpoints 1

1. - All cause mortality at ICU discharge, hospital discharge at day90; - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay; - IFHs day28; - HFD day90; - VFDs day 28; - VasoFDs at day28; - AFDs day28; - ICU acquired weakness at 7, 28 and 90days or hospital discharge defined by MRC Scale; - Occurrence of protocol related adverse events at day28.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Di Modena

Sponsor organisation

Azienda Ospedaliero Universitaria Di Modena

Address

Largo Del Pozzo 71

City

Modena

Postcode

41124

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Massimo Girardis

Public contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Massimo Girardis

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications