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

Polyneuropathies Clinical Trial

— CIPNM  

Official title:

The Impact of Early Treatment With IgM-enriched IVIG on Critical Illness Polyneuropathy and/or Myopathy in Patients With Multiple Organ Failure and SIRS/Sepsis: A Prospective, Randomized, Placebo-controlled, Double-blinded Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01867645
• Other study ID #: CIPNM
• Status: Terminated
• Phase: Phase 1
• First received: May 23, 2013
• Last updated: May 29, 2013
• Start date: December 2004
• Est. completion date: April 2011

Study information

• Verified date: May 2013
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: April 2011
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Critically ill patients with failure of at least 2 organ systems diagnosed with SIRS or sepsis fulfilling the following inclusion criteria will be included in this study.

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

Exclusion Criteria:

The inclusion criteria have to be met at the time of enrolment into the study, i.e. at the start of the baseline period. Patients with any of the following conditions will be excluded from the study:

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Illness
• Multiple Organ Failure
• Polyneuropathies

Intervention

Drug:
• 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.
• 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

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of Vienna	Biotest Pharma GmbH, National Bank of Austria

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Effect of early IVIG versus placebo on mortality from any cause within a 28-day period	This secondary outcome aimed to assess the effect of early IVIG versus placebo on mortality from any cause within a 28-day period.	28 days	No
Secondary	Effect of early IVIG versus placebo on length of the ICU stay.	This secondary outcome aimed to assess the effect of early IVIG versus placebo on the length of the ICU stay. Length of ICU stay is defined as the time difference difference between admission of the patient to the ICU and discharge to a (non-ICU) ward or death. This outcome will be assessed an the day of ICU discharge.	ICU stay, an expected average of 30 days	No