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

NCT ID: NCT01867645

Last Updated: 2013-06-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2011-04-30

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.

Detailed Description

Background: 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 will be to assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective setting.

Design: Prospective, randomized, double-blinded and placebo-controlled trial

Setting: Eight-bed medical ICU of a university hospital.

Participants: Critically ill patients will be screened for eligibility defined as multiple organ failure (MOF) and SIRS/sepsis. Patients fulfilling these criteria will be further assessed by a neurologist for clinical signs of CIPNM.

Critically ill patients with multiple organ failure (MOF), SIRS/sepsis, and early clinical signs of CIPNM will be randomized.

Conditions

Polyneuropathies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

IgM-enriched Intravenous Immunoglobulins

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

Group Type: ACTIVE_COMPARATOR

IgM-enriched Intravenous Immunoglobulins

Intervention Type: 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.

Human Albumin

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

Group Type: PLACEBO_COMPARATOR

Human Albumin

Intervention Type: 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

Interventions

IgM-enriched Intravenous Immunoglobulins

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.

Intervention Type: DRUG

Human Albumin

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

Intervention Type: DRUG

Other Intervention Names

IVIG; IgM-enriched IVIG; Placebo

Eligibility Criteria

Inclusion Criteria

1. Age Range: 18 - 80 years

2. written information and consent as early as possible

3. Male and female patients

4. 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:

Patients have to meet at least three of the following four criteria:

• core temperature >38 or <36°C
• heart rate >90 beats /min, except medical conditions known to increase heart rate
• respiratory rate >20 breaths/min or a PaCO2 of <32mm Hg or the use of mechanical ventilation for an acute respiratory process
• a white- cell count of>12.000 cells/mm3 or <4.000 cells/mm3 or a differential count showing >10% immature neutrophils

Sepsis:

Known or suspected infection evidenced by one or more of the following:

• white cells or bacteria in a normally sterile body fluid
• perforated viscus
• radiographic evidence of pneumonia in the association with the production of purulent sputum
• a syndrome associated with a high risk of infection

1. Age < 18 years or > 80 years

2. Weight >135 kg

3. Pregnancy or breast-feeding

4. Patients with known absolute IgA-deficiency with proven antibody formation against IgA

5. Patients with known IVIG-intolerability

6. Patients with known pre-existing neuromuscular disorders will not be included. Patients with documented pre-existing severe polyneuropathy will be excluded.

7. 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.

8. 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

9. Patients not expected to survive 28 days because of uncorrectable medical condition, such as poorly controlled neoplasma or other end-stage disease

10. Moribund state in which death is perceived to be imminent

11. HIV infection in association with a last known CD4 count of<50/mm3

12. Prediction, based on clinical judgement, that the patient will require chronic ventilatory support for non-respiratory reasons (e.g. neuromuscular disease, paraplegia

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biotest Pharma GmbH

UNKNOWN

Sponsor Role: collaborator

National Bank of Austria

OTHER_GOV

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Christian Madl

Univ.-Prof.Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christian Madl, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna

Vienna, Vienna, Austria

Countries

Austria

References

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.

Reference Type: DERIVED

PMID: 24088271 (View on PubMed)

Other Identifiers

CIPNM

Identifier Type: -

Identifier Source: org_study_id