Septic ShockPhase 4NCT02875236
Vasculopathic Injury and Plasma as Endothelial Rescue in Septic Shock Trial. VIPER-Sepsis (EudraCT no. 2016-000707-81)
A Phase 4 study testing OctaplasLG® and Ringer-acetat in people with Septic Shock, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
Efficacy and safety of octaplasLG® administration vs. crystalloids (standard) in patients with septic shock - a randomized, controlled, open-label investigator-initiated pilot trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- OctaplasLG® and Ringer-acetat
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2016to 8 Nov 2016
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult intensive care patients AND
- Septic shock requiring infusion of vasopressor/inotropic agents to maintain blood pressure as defined in international guidelines AND
- Consent obtainable from patient or by proxy (independent physicians and/or next of kin)
Who cannot join
- Documented refusal of blood transfusion OR
- Treatment with GPIIb/IIIa inhibitors < 24h from screening OR
- Withdrawal from active therapy OR
- Previously within 30 days included in a randomised trial, if known at the time of enrolment OR
- Known Immunoglobulin A deficiency with documented antibodies against Immunoglobulin A OR
- Known hypersensitivity to OctaplasLG: the active substance, any of the excipients (Sodium citrate dihydrate, Sodium dihydrogenphosphate dihydrate or Glycine) or residues from the manufacturing process (Tri (N-Butyl) Phosphate (TNBP) and Octoxynol (Triton X-100)) OR
Show all 9Show fewer
- Known severe deficiencies of protein S OR
- Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative urine-hCG) OR
- Severe cirrhotic hepatic failure with expected need for treatment with terlipressin
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of OctaplasLG Administration vs. Crystalloids (Standard) in Patients With Septic Shock - a Randomized, Controlled, Open-label Investigator-initiated Pilot Trial
Efficacy and safety of octaplasLG® administration vs. crystalloids (standard) in patients with septic shock - a randomized, controlled, open-label investigator-initiated pilot trial.
Read the detailed description
Recently a great interest in the role of the endothelium in the pathophysiology of sepsis has been introduced. The endothelium is coated by a "thick" endothelial glycocalyx protecting it from becoming activated and prevents capillary leakage. The glycocalyx binds approximately 1-1.5 litres of the plasma portion of the circulating blood and regulates the dynamic exchange between the intra -and extravascular space, therefore, functioning both as a barrier and as a mechano transducer. Damage to the glycocalyx is caused by major trauma, major surgery, or ischemia and reperfusion injury, and resulting in vascular leakage. Damage to the endothelium is further augmented by resuscitation of crystalloids and colloids as well as related to bleeding. Thawed fresh frozen plasma may cause a further "inflammatory hit" towards the glycocalyx and endothelium. The degradation of the glycocalyx increases endothelial permeability with edema formation entitled 'the endothelial leakage syndrome', and resulting in the development of hypotension, pulmonary complications, abdominal compartment syndrome, multi-organ failure and death.
The current strategy for maintaining the intravascular volume in patients with acute critical illness focuses on the administration of crystalloids, such as Ringer-Acetate, and natural colloids. Crystalloids, especially, are known to extravasate and cause edema, which is associated with hypoperfusion and compromised vital organ function by the increased tissue pressure that limits oxygen delivery, and ultimately leading to the complications described above. Until recently, synthetic colloids were the preferred choice of fluids for these patients, but a Scandinavian study in patients with severe sepsis and septic shock (6S trial) demonstrated an increased mortality in patients receiving synthetic colloids, thereby, establishing the adverse effect of such a strategy. Consequently, new resuscitation fluids are needed, preferably not only to support the intravascular volume, but also to support and restore the endothelial integrity.
- Conditions
- Septic Shock
- Being tested
- OctaplasLG®, Ringer-acetat
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OctaplasLG®Drug
Also called OctaplasLG
OctaplasLG is an donor plasma product pooled from approximately 1000 single donor units. It possesses unique features when compared to standard fresh frozen plasma, such as having standardized concentrations of natural pro- and anti-coagulation factors, a standardized volume as well as being pathogen free. The manufacturing method of OctaplasLG removes immune complexes and cells in several steps of microfiltration in addition to viral, bacterial and prion pathogen inactivation by immune neutralization. OctaplasLG should reduce the "inflammatory hit" on the endothelium, including the glycocalyx, by having standardized levels of coagulation proteins, which can give more sustainable support to the endothelial regeneration as compared to standard fresh frozen plasma.
Ringer-acetatDrug
Also called Ringer
Crystalloid used as standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Ringer-acetat Receives: Drug: OctaplasLG® |
| Intervention | Active comparator | OctaplasLG® Receives: Drug: Ringer-acetat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microvascular perfusion
Change in microvascular perfusion as evaluated by sidestream darkfield (SDF; MicroVision Medical, Amsterdam, The Netherlands) imaging technique.
Measured: 6 hours after inclusion
Endothelial activation and damage
Change in biomarkers indicative of endothelial activation and damage (soluble E-selectin, syndecan-1, thrombomodulin, soluble VE-cadherin, nucleosomes)
Measured: 6 hours after inclusion
Secondary outcomes (8)
Mortality
Difference in mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids)
Measured: From 6 hours until 90 days
Length of stay in Intensive Care Unit
Length of stay in the Intensive Care Unit
Measured: through study completion, an average of 1 month
Vasopressors
Days on vasopressors
Measured: through study completion, an average of 1 month
Ventilator
Days on ventilator
Measured: through study completion, an average of 1 month
Bleeding
Bleeding requiring > 2 RBC / day
Measured: 1 week
SAR
Severe adverse reactions, defined as symptomatic thromboembolism
Measured: 30 days
TACO
Transfusion associated circulatory overload
Measured: 30 days
TRALI
Transfusion Related Acute Lung Injury
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2016 (estimated)
- Study start1 Sep 2016
- Primary completion8 Nov 2016
- Study completion8 Nov 2016
Why it stopped: Changing the study design
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Octapharma
- Responsible party
- Principal investigator, Thomas Bech Jørgensen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Per I Johansson, MD, Study director, University of Copenhagen, Rigshospitalet, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02875236
- Sponsor's protocol ID
- Viper Sepsis
- Status last verified
- Jan 2018
- First submitted
- 11 Aug 2016
- Last updated
- 9 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: All data from the study will be made public in a peer review journal after last inclusion. But no individual participant data (IPD) will be public.
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of OctaplasLG Administration vs. Crystalloids (Standard) in Patients With Septic Shock - a Randomized, Controlled, Open-label Investigator-initiated Pilot Trial
- ClinicalTrials.gov ID
- NCT02875236
- Acronym / sponsor ID
- Viper Sepsis
- Conditions
- Septic Shock
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Changing the study design
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Octapharma
- Study start
- 1 Sep 2016 (actual)
- Primary completion
- 8 Nov 2016 (actual)
- Study completion
- 8 Nov 2016 (actual)
- First posted
- 23 Aug 2016 (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.
Efficacy and safety of octaplasLG® administration vs. crystalloids (standard) in patients with septic shock - a randomized, controlled, open-label investigator-initiated pilot trial.
Detailed description
Recently a great interest in the role of the endothelium in the pathophysiology of sepsis has been introduced. The endothelium is coated by a "thick" endothelial glycocalyx protecting it from becoming activated and prevents capillary leakage. The glycocalyx binds approximately 1-1.5 litres of the plasma portion of the circulating blood and regulates the dynamic exchange between the intra -and extravascular space, therefore, functioning both as a barrier and as a mechano transducer. Damage to the glycocalyx is caused by major trauma, major surgery, or ischemia and reperfusion injury, and resulting in vascular leakage. Damage to the endothelium is further augmented by resuscitation of crystalloids and colloids as well as related to bleeding. Thawed fresh frozen plasma may cause a further "inflammatory hit" towards the glycocalyx and endothelium. The degradation of the glycocalyx increases endothelial permeability with edema formation entitled 'the endothelial leakage syndrome', and resulting in the development of hypotension, pulmonary complications, abdominal compartment syndrome, multi-organ failure and death.
The current strategy for maintaining the intravascular volume in patients with acute critical illness focuses on the administration of crystalloids, such as Ringer-Acetate, and natural colloids. Crystalloids, especially, are known to extravasate and cause edema, which is associated with hypoperfusion and compromised vital organ function by the increased tissue pressure that limits oxygen delivery, and ultimately leading to the complications described above. Until recently, synthetic colloids were the preferred choice of fluids for these patients, but a Scandinavian study in patients with severe sepsis and septic shock (6S trial) demonstrated an increased mortality in patients receiving synthetic colloids, thereby, establishing the adverse effect of such a strategy. Consequently, new resuscitation fluids are needed, preferably not only to support the intravascular volume, but also to support and restore the endothelial integrity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Drug: OctaplasLG®Ringer-acetat |
| Intervention | Active comparator | Drug: Ringer-acetatOctaplasLG® |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult intensive care patients AND
- Septic shock requiring infusion of vasopressor/inotropic agents to maintain blood pressure as defined in international guidelines AND
- Consent obtainable from patient or by proxy (independent physicians and/or next of kin)
Key exclusion criteria (9 listed)
- Documented refusal of blood transfusion OR
- Treatment with GPIIb/IIIa inhibitors < 24h from screening OR
- Withdrawal from active therapy OR
- Previously within 30 days included in a randomised trial, if known at the time of enrolment OR
- Known Immunoglobulin A deficiency with documented antibodies against Immunoglobulin A OR
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 |
|---|---|---|
| OctaplasLG®Also: OctaplasLGOctaplasLG is an donor plasma product pooled from approximately 1000 single donor units. It possesses unique features when compared to standard fresh frozen plasma, such as having standardized concentrations of natural pro- and anti-coagulation factors, a standardized volume as well as being pathogen free. The manufacturing method of OctaplasLG removes immune complexes and cells in several steps of microfiltration in addition to viral, bacterial and prion pathogen inactivation by immune neutralization. OctaplasLG should reduce the "inflammatory hit" on the endothelium, including the glycocalyx, by having standardized levels of coagulation proteins, which can give more sustainable support to the endothelial regeneration as compared to standard fresh frozen plasma. | Drug | Control |
| Ringer-acetatAlso: RingerCrystalloid used as standard of care. | Drug | Intervention |
Primary outcome
Microvascular perfusion
Time frame: 6 hours after inclusion
Change in microvascular perfusion as evaluated by sidestream darkfield (SDF; MicroVision Medical, Amsterdam, The Netherlands) imaging technique.
Endothelial activation and damage
Time frame: 6 hours after inclusion
Change in biomarkers indicative of endothelial activation and damage (soluble E-selectin, syndecan-1, thrombomodulin, soluble VE-cadherin, nucleosomes)
8 secondary outcomes
Mortality
Time frame: From 6 hours until 90 days
Length of stay in Intensive Care Unit
Time frame: through study completion, an average of 1 month
Vasopressors
Time frame: through study completion, an average of 1 month
Ventilator
Time frame: through study completion, an average of 1 month
Bleeding
Time frame: 1 week
SAR
Time frame: 30 days
TACO
Time frame: 30 days
TRALI
Time frame: 30 days
Results and safety
The study was stopped early (reason given: Changing the study design). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2018.
- Individual participant dataSharing planned: No. All data from the study will be made public in a peer review journal after last inclusion. But no individual participant data (IPD) will be public.
Related trials for Septic Shock
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
Not yet recruitingObservational study
Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
Sepsis, Septic Shock Hyperdynamic
RecruitingObservational study
Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Sepsis
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.
Per I Johansson, MD study director
University of Copenhagen, Rigshospitalet, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing OctaplasLG® and Ringer-acetat in people with Septic Shock, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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 3 inclusion and 9 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 9 Jan 2018. 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 Denmark. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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: Changing the study design). 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?
Microvascular perfusion (time frame: 6 hours after inclusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jan 2018.