The Impact of IVIG Treatment on Critical Illness Polyneuropathy and/or Myopathy in Patients With MOF and SIRS/Sepsis

NCT01867645 | Terminated Phase 1

• 1 other identifier: CIPNM
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication of critical illness. Retrospective data suggest that early application of IgM-enriched intravenous immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary objective was to assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective setting.

Conditions

Polyneuropathies

Keywords

Critical illness; Critical illness polyneuropathy and/or myopathy; Intravenous immunoglobulins; Multiple organ failure; SIRS; Sepsis

Outcome Measures

Primary Outcomes (1)

• Effect of early IVIG versus placebo on CIPNM on day 14

  The primary outcome was to assess the effect of early IVIG (IgM-enriched Intravenous immunoglobulins) versus placebo to mitigate CIPNM in critically ill patients as assessed by the CIPNM severity sum score on day 14. The CIPNM severity sum score is based on electrophysiological stimulation of the median, ulnar, and tibial nerves on days 0, 4, 7, 14 and on the histological evaluation of muscle biopsies on days 0 and 14 and ranged from 0 (no CIPNM) to 8 (very severe CIPNM).

  day 14

Secondary Outcomes (2)

• Effect of early IVIG versus placebo on mortality from any cause within a 28-day period

  28 days

• Effect of early IVIG versus placebo on length of the ICU stay.

  ICU stay, an expected average of 30 days

Study Arms (2)

IgM-enriched Intravenous Immunoglobulins

ACTIVE COMPARATOR

IgM-enriched IVIG (Pentaglobin, Biotest Pharma GmbH, Dreieich, Germany) at a dose of 0.25g/kg body weight/day as a continuous intravenous infusion at a rate of 2g/h over a period of 3 days

Drug: IgM-enriched Intravenous Immunoglobulins

Human Albumin

PLACEBO COMPARATOR

Human albumin 1% (Biotest Pharma GmbH, Dreieich, Germany) as placebo at a dose of 0.25g/kg body weight/day as a continuous intravenous infusion at a rate of 2g/h over a period of 3 days

Drug: Human Albumin

Interventions

IgM-enriched Intravenous Immunoglobulins DRUG

IgM-enriched IVIG (Pentaglobin, Biotest Pharma GmbH, Dreieich, Germany) at a dose of 0.25g/kg body weight/day as a continuous intravenous infusion at a rate of 2g/h over a period of 3 days.

Also known as: IVIG, IgM-enriched IVIG

IgM-enriched Intravenous Immunoglobulins

Human Albumin DRUG

Human albumin 1% (Biotest Pharma GmbH, Dreieich, Germany) as placebo at a dose of 0.25g/kg body weight/day as a continuous intravenous infusion at a rate of 2g/h over a period of 3 days

Also known as: Placebo

Human Albumin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age Range: 18 - 80 years
• written information and consent as early as possible
• Male and female patients
• Clinical signs of incipient CIPNM:
• decreased tendon reflexes as compared to the admission examination at the ICU
• or weakness in responsive and co-operative patients as compared to the ad-mission examination at the ICU
• or signs of incipient muscular atrophy as compared to the admission examination at the ICU
• Organ failure:
• Patients have to meet at least two of the following 5 criteria:
• cardiovascular system dysfunction: arterial systolic blood pressure\<90mm Hg, or mean arterial pressure \< 70mm Hg for at least one hour despite adequate fluid resuscitation, adequate intravascular volume status or the use of vasopressors in an attempt to maintain a systolic blood pressure \>90mm Hg or a mean arterial pressure \>70mm Hg.
• kidney dysfunction: Urine output \< 0,5ml/kg body weight/ hour for 1 hour, despite adequate fluid resuscitation
• respiratory system dysfunction: Ratio of PaO2 to FiO2 \< 250 in the presence of other dysfunctional organs or systems
• hematologic dysfunction: Platelet count \<80.000/mm3 or decreased by 50% in the 3 days preceding enrollment (in the absence of liver cirrhosis or previously known hematological disease)
• metabolic dysfunction: In case of unexplained metabolic acidosis - pH\<7,30 or base deficit \>5.0mmol/ litre in association with a plasma lactate level \>1,5 times of the upper normal limit
• SIRS:

You may not qualify if:

• Age \< 18 years or \> 80 years
• Weight \>135 kg
• Pregnancy or breast-feeding
• Patients with known absolute IgA-deficiency with proven antibody formation against IgA
• Patients with known IVIG-intolerability
• Patients with known pre-existing neuromuscular disorders will not be included. Patients with documented pre-existing severe polyneuropathy will be excluded.
• Patients with known diseases of the peripheral nerval system and patients with pre-existing disease of the central nerval system with relevant impairment of the motor function.
• Patients with relevant pulmonary edema secondary to severe heart failure will be excluded because of the relatively high infusion volume (5ml /kg body weight per day over 3 days) determined by the study medication
• Patients not expected to survive 28 days because of uncorrectable medical condition, such as poorly controlled neoplasma or other end-stage disease
• Moribund state in which death is perceived to be imminent
• HIV infection in association with a last known CD4 count of\<50/mm3
• Prediction, based on clinical judgement, that the patient will require chronic ventilatory support for non-respiratory reasons (e.g. neuromuscular disease, paraplegia

Sponsors & Collaborators

• Medical University of Vienna: lead
• Biotest Pharma GmbH: collaborator
• National Bank of Austria: collaborator

Study Sites (1)

Medical University of Vienna

Vienna, Vienna, 1090, Austria

Location

Related Publications (1)

• Brunner R, Rinner W, Haberler C, Kitzberger R, Sycha T, Herkner H, Warszawska J, Madl C, Holzinger U. Early treatment with IgM-enriched intravenous immunoglobulin does not mitigate critical illness polyneuropathy and/or myopathy in patients with multiple organ failure and SIRS/sepsis: a prospective, randomized, placebo-controlled, double-blinded trial. Crit Care. 2013 Oct 2;17(5):R213. doi: 10.1186/cc13028.

  PMID: 24088271 DERIVED

MeSH Terms

Conditions

Polyneuropathies; Critical Illness; Multiple Organ Failure; Sepsis

Interventions

Immunoglobulins, Intravenous; Serum Albumin, Human

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Infections; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Serum Albumin; Albumins

Study Officials

• Christian Madl, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: Univ.-Prof.Dr.

Study Record Dates

• First Submitted: May 23, 2013
• First Posted: June 4, 2013
• Study Start: December 1, 2004
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2011
• Last Updated: June 4, 2013

Record last verified: 2013-05

Locations

AU (1)