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

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Massimo Girardis

Stay on Your Current Meds

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Eligibility Criteria

Inclusion Criteria

Age > 18 years;

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;

IgM-titers< 60mg/dl (or < 20% of the lower threshold value of local laboratory) within24hours from shock occurrence.

Treatment Details

Interventions

IgM-enriched polyclonal immunoglobulins (Immunoglobulin)

Participant Groups

2Treatment groups

Experimental Treatment

Active Control

Group I: IgM titer-based treatmentExperimental Treatment1 Intervention

The treatment with IgM preparation will be initiated as soon as possible after randomization (maximum allowed starting time 12h after randomization). The calculation of the dose is based on IgM single compartment distribution. The first dose of IgM preparation will be calculated on IgM serum concentration obtained within 24 hours after shock appearance to achieve serum titers above 100mg/dl. In the next days, the daily IgM preparation dose will be assessed individually on the basis of IgM serum titers assessment performed in the morning with the purpose of maintaining IgM serum titers above 100 mg/dl, up to discontinuation of vasoactive drugs or day 7 after enrolment. Daily, the calculated dose will be administered in 24 hours in continuous infusion with a maximum infusion rate of 0,4 ml/kg per hour (20mg/kg per hour). IgM preparation will be administered up to the withdrawal of vasoactive drugs with a maximum allowed of 7 days of therapy and a maximum dose of 350mg/Kg/day.

Group II: IgM Flat treatmentActive Control1 Intervention

The IgM treatment will be initiated as soon as possible after randomization (maximum allowed starting time 12h after randomization). The dose of IgM preparation will be 250mg/kg for 3 days, the dose will be administered in 24 hours in continuous infusion with a maximum infusion rate of 0,4 ml/kg (20mg/kg per hour) until reaching 250mg/kg.