PolyneuropathiesPhase 1CIPNMNCT01867645
The Impact of IVIG Treatment on Critical Illness Polyneuropathy and/or Myopathy in Patients With MOF and SIRS/Sepsis
A Phase 1 study testing IgM-enriched Intravenous Immunoglobulins and Human Albumin in people with Polyneuropathies, run by Medical University of Vienna at 1 site in Austria.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Polyneuropathies
- What is being tested?
- IgM-enriched Intravenous Immunoglobulins and Human Albumin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteAustria
- Study dates
- Dec 2004to Apr 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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
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- 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
Who cannot join
- 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:
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- IgM-enriched Intravenous Immunoglobulins, Human Albumin
- Keywords
- Critical illness, Critical illness polyneuropathy and/or myopathy, Intravenous immunoglobulins, Multiple organ failure, SIRS, Sepsis
- Medical subject headings
- Polyneuropathies, Critical Illness, Multiple Organ Failure, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IgM-enriched Intravenous ImmunoglobulinsDrug
Also called IVIG, IgM-enriched IVIG
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 AlbuminDrug
Also called Placebo
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Human Albumin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: day 14
Secondary outcomes (2)
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.
Measured: 28 days
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.
Measured: ICU stay, an expected average of 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2013 (estimated)
- Study startDec 2004
- Primary completionApr 2009
- Study completionApr 2011
Why it stopped: The trial was terminated early due to futility in reaching the primary endpoint.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PolyneuropathiesStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- Biotest Pharma GmbH, National Bank of Austria
- Responsible party
- Principal investigator, Christian Madl, Medical University of Vienna
- Investigators
- Christian Madl, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01867645
- Sponsor's protocol ID
- CIPNM
- Acronym
- CIPNM
- Status last verified
- May 2013
- First submitted
- 23 May 2013
- Last updated
- 4 Jun 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 24088271
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01867645
- Acronym / sponsor ID
- CIPNM / CIPNM
- Conditions
- Polyneuropathies
- Keywords
- Critical illness, Critical illness polyneuropathy and/or myopathy, Intravenous immunoglobulins, Multiple organ failure, SIRS, Sepsis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was terminated early due to futility in reaching the primary endpoint.
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Collaborators
- Biotest Pharma GmbH, National Bank of Austria
- Study start
- Dec 2004
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 4 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IgM-enriched Intravenous Immunoglobulins | Active comparator | Drug: IgM-enriched Intravenous ImmunoglobulinsIgM-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 | Placebo comparator | Drug: Human AlbuminHuman 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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.
- Age Range: 18 - 80 years
- written information and consent as early as possible
- Male and female patients
- Clinical signs of incipient CIPNM:
Key exclusion criteria (13 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IgM-enriched Intravenous ImmunoglobulinsAlso: IVIG, IgM-enriched IVIGIgM-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 AlbuminAlso: PlaceboHuman 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 |
Primary outcome
Effect of early IVIG versus placebo on CIPNM on day 14
Time frame: 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).
2 secondary outcomes
Effect of early IVIG versus placebo on mortality from any cause within a 28-day period
Time frame: 28 days
Effect of early IVIG versus placebo on length of the ICU stay.
Time frame: ICU stay, an expected average of 30 days
Results and safety
The study was stopped early (reason given: The trial was terminated early due to futility in reaching the primary endpoint.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2013.
- Derived from this study: PubMed 24088271Brunner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Madl, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IgM-enriched Intravenous Immunoglobulins and Human Albumin in people with Polyneuropathies, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The trial was terminated early due to futility in reaching the primary endpoint.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of early IVIG versus placebo on CIPNM on day 14 (time frame: day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01867645, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2013.