Effects on Microcirculation of IgGAM in Severe Septic/Septic Shock Patients.

NCT02655133 | Completed Phase 2 DMC

• 1 other identifier: IgGAM-CLRZ-2014
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

IgM-enriched immunoglobulins (IgGAM; Pentaglobin ® ) are new therapy for sepsis and septic shock since they support immune system especially in case of " immunoparalysis" . However IgGAM isn't commonly prescribed, few centres use it as routine in severe infections and there aren't any guidelines to determine how and when to use them. Microcirculatory dysfunction is a crucial aspect in the pathogenesis of sepsis-induced organ dysfunction, resulting in hypoperfusion and tissue hypoxia. Unpublished clinical data suggest a beneficial effect of IgGAM at microvascular level proved with near infrared spectroscopy and Vascular occlusion test (VOT). This study is a double blind phase II prospective randomised controlled trial that will include patients admitted to the Intensive Care Unit of the University Hospital "Ospedali Riuniti" of Ancona, after no more than 24 hours from development of severe sepsis or septic shoc. Patients will be randomized into two groups (treaties and controls): patients in group of the treaties will be submitted to infusion of IgGAM conjugate (Pentaglobin ®) at dosage of 250 mg/kg IV (5 mL/kg) per day (rate of 0.4 mL/kg/h), for 72 hours. The controls will receive equal amount of physiological NaCl solution (0.9%) as placebo. Neither the patient nor the staff nurses and MD will be aware of the group and of the treatment applied. IgGAM solutions or NaCl 0.9% will be provided by the hospital pharmacy in similar bags. The remaining treatments will not be changed in any way and will be at the discretion of the doctor who's in charge of the patient. All patients of the two groups will receive the optimal therapy for their conditions, according to good medical clinical practice (GMP), with appropriate antibiotic therapy, vasoactive and infusional therapy

Conditions

Severe Sepsis; Septic Shock

Outcome Measures

Primary Outcomes (1)

• Perfused vessel density (PVD)

  The perfused vessel density (PVD), unity of measure mm/mm2, is detected in vivo by Incident Dark Field Imaging at sublingual microcirculation. It represents the quantity of well perfused vessels at microcirculatory level.

  72 hours

Secondary Outcomes (4)

• StO2 upload

  72 hours

• Microcirculatory Flow Index (MFI)

  72 hours

• Arterial blood lactate

  72 hours

• SOFA score (Sequential Organ Failure Assessment)

  72 hours

Study Arms (2)

Pentaglobin®

ACTIVE COMPARATOR

Patients will receive Immunoglobulins IgGAM (Pentaglobin®) at dosage of 250 mg/kg IV (5 mL/kg) per day (rate of 0.4 mL/kg/h), for 72 hours. Microcirculation will be monitored with sublingual microcirculation device (Cytocam®) and Near InfraRed Specrotcopy (NIRS, Hutchinson®).

Drug: Pentaglobin®

Physiologic Solution

PLACEBO COMPARATOR

Patients will receive physiologic solution (NaCl 0.9%) at a dosage of 5 ml/Kg per day for 72 hours. Microcirculation will be monitored with sublingual microcirculation device (Cytocam®) and Near InfraRed Specrotcopy (NIRS, Hutchinson®)

Drug: Physiologic solution

Interventions

Pentaglobin® DRUG

Immunoglobulins that will be used are IgM enriched and will be infused at 5 ml/Kg/day for 3 days.

Also known as: IgGAM

Pentaglobin®

Physiologic solution DRUG

Physiologic solution will be infused and will be infused at 5 ml/Kg/day for 3 days.

Physiologic Solution

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• severe sepsis
• septic shock

You may not qualify if:

• pregnant women
• severe sepsis/septic shock for more than 24 hours
• chronic renal failure
• terminal state with a life expectancy of less than 24 hours
• contraindications to treatment with IgGAM
• lack of informed consent will be excluded.

Sponsors & Collaborators

• Università Politecnica delle Marche: lead

Study Sites (1)

University ICU, AOU Ospedali Riuniti Ancona

Torrette Di Ancona, Ancona, 60126, Italy

Location

Related Publications (1)

• Domizi R, Adrario E, Damiani E, Scorcella C, Carsetti A, Giaccaglia P, Casarotta E, Gabbanelli V, Pantanetti S, Lamura E, Ciucani S, Donati A. IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial. Ann Intensive Care. 2019 Dec 3;9(1):135. doi: 10.1186/s13613-019-0609-5.

  PMID: 31797105 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

pentaglobulin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Abele Donati, MD

  AOU Ospedali Riuniti di Ancona, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology

Study Record Dates

• First Submitted: January 7, 2016
• First Posted: January 13, 2016
• Study Start: January 1, 2016
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: May 24, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)