NCT04182737: IgM-FAT

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

Status unknown Phase 3 Last updated 6 May 2021

What this trial tests

Phase 3 trial testing IgM-enriched polyclonal immunoglobulins titer-based treatment in Shock, Septic in 356 participants. Status unknown.

Timeline

1 May 2020

Primary endpoint
28 February 2022

31 March 2022

Quick facts

Lead sponsor	Massimo Girardis
Phase	Phase 3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	356
Start date	1 May 2020
Primary completion	28 February 2022
Estimated completion	31 March 2022
Sites	1 location across Italy

Drugs / interventions tested

• IgM-enriched polyclonal immunoglobulins titer-based treatment — full drug profile →
• IgM-enriched polyclonal immunoglobulins Flat treatment — full drug profile →

Conditions studied

• Shock, Septic — all drugs for Shock, Septic →
• Sepsis — all drugs for Sepsis →
• Hypoglobulinemia — all drugs for Hypoglobulinemia →

Sponsor

Massimo Girardis — full company profile →

Who can join

18 and older, any sex, with Shock, Septic or Sepsis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Treatment Advances in Sepsis and Septic Shock: Modulating Pro- and Anti-Inflammatory Mechanisms.
   Marques A, Torre C, Pinto R, Sepodes B, et al · · 2023 · cited 42× · PMID 37109229 · DOI 10.3390/jcm12082892
2. Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis.
   Nierhaus A, Berlot G, Kindgen-Milles D, Müller E, et al · · 2020 · cited 38× · PMID 33026597 · DOI 10.1186/s13613-020-00740-1
3. Sepsis-induced immunosuppression: mechanisms, biomarkers and immunotherapy.
   Gao X, Cai S, Li X, Wu G. · · 2025 · cited 29× · PMID 40364841 · DOI 10.3389/fimmu.2025.1577105
4. Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial).
   Biagioni E, Tosi M, Berlot G, Castiglione G, et al · · 2021 · cited 11× · PMID 33574139 · DOI 10.1136/bmjopen-2019-036616
5. Clinical practice of sepsis-induced immunosuppression: Current immunotherapy and future options.
   Pei F, Gu B, Miao SM, Guan XD, et al · · 2024 · cited 10× · PMID 38040590 · DOI 10.1016/j.cjtee.2023.11.001
6. Adjunctive Immunotherapy With Polyclonal Ig-M Enriched Immunoglobulins for Septic Shock: From Bench to Bedside. The Rationale for a Personalized Treatment Protocol.
   Busani S, Roat E, Tosi M, Biagioni E, et al · · 2021 · cited 5× · PMID 33681248 · DOI 10.3389/fmed.2021.616511
7. Effect of Intravenous IgM-Enriched Immunoglobulins on Presepsin and Other Sepsis Biomarkers.
   Scarpati G, Baldassarre D, Tripepi G, Boffardi M, et al · · 2021 · cited 1× · PMID 34566642 · DOI 10.3389/fphar.2021.717349
8. Bioprocessing method is a critical factor for IgM oligomerization
   Üzülmez Ö, Hawlin V, John MM, Stadlbauer K, et al · · 2026 · DOI 10.21203/rs.3.rs-9343237/v1