Efficacy and Safety of Therapy With IgM-enriched Immunoglobulin With a Personalized Dose vs Standard Dose in Patients With Septic Shock.

• Status: Recruiting
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: All

Summary

In patients with septic shock, low levels of circulating immunoglobulins are common and they are kinetic, particularly of immunoglobulin M (IgM), seems to be related with clinical outcome. These observations, combined with the pivotal role of immunoglobulins on host immune response to infections, led to consider therapy with polyclonal intravenous immunoglobulins a promising option in patients with septic shock.

IgM-enriched preparations have been used since now most of all at a standard dose recommended by the producer although a more tailored approach may improve patients' outcomes.

This study hypothesizes that in patients with septic shock and low IgM immunoglobulins titers at shock onset, adjunctive treatment with a personalized dose of IgM-enriched immunoglobulins based on IgM serum titers of the patient may reduce mortality compared to a standard dose of IgM-enriched immunoglobulins. The study is designed as a multicentre, national, interventional, randomized, single-blinded, prospective, investigator-sponsored, two arms study. Patients will be randomly assigned to IgM titer-based treatment or flat treatment group in a 1:1 ratio. One group of patients will receive IgM-enriched immunoglobulins adjunctive treatment in a standard dose of 250mg/kg for 3 days. The other group will receive IgM-enriched immunoglobulins adjunctive treatment in a variable dose calculated taking note of the extent of IgM deficit, in order to achieve an IgM threshold value of 100 mg/dL or above. IgM preparation will be administered in this group up to the withdrawal of vasoactive drugs with a maximum allowed of 7 days. The confirmation of the efficacy of a tailored strategy for IgM-enriched immunoglobulin administration in reducing the mortality rate among patients with septic shock and low IgM titers will lead to a revision of the current clinical practice in the use of this adjunctive treatment.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massimo Girardis
• Treatments: Antibodies; Immunoglobulins; Immunoglobulins, Intravenous

Criteria

Inclusion Criteria:

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) within24hours from shock occurrence.

Exclusion Criteria:

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 of withdrawal of informed consent.