Clinical Trials Register

Summary
EudraCT Number:	2016-000707-81
Sponsor's Protocol Code Number:	VIPER-SEPSIS
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-02-19
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2016-000707-81

A.3

Full title of the trial

Vasculopathic Injury and Plasma as Endothelial Rescue in septic shock (SEPSIS) trial

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy and safety of octaplasLG® administration vs. crystalloids (standard) in patients with septic shock – a randomized, controlled, assessor-blinded investigator-initiated pilot trial

A.3.2

Name or abbreviated title of the trial where available

VIPER-SEPSIS trial

A.4.1

Sponsor's protocol code number

VIPER-SEPSIS

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Section for Transfusion Medicine, Capitol Region Blood Bank
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Octapharma AG
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Section for Transfusion Medicine, Capitol Region Blood Bank
B.5.2	Functional name of contact point	Pär I. Johansson
B.5.3	Address:
B.5.3.1	Street Address	Blegdamsvej 9
B.5.3.2	Town/ city	Copenhagen
B.5.3.3	Post code	DK-2100
B.5.3.4	Country	Denmark
B.5.4	Telephone number	4535452030
B.5.6	E-mail	per.johansson@regionh.dk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	octaplasLG
D.2.1.1.2	Name of the Marketing Authorisation holder	Octapharma AG Sweden
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Octaplas
D.3.9.1	CAS number	N/A
D.3.9.3	Other descriptive name	HUMAN PLASMA POOLED AND TREATED FOR VIRUS INACTIVATION
D.3.9.4	EV Substance Code	SUB14915MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Yes
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ringer-acetat
D.2.1.1.2	Name of the Marketing Authorisation holder	Fresenius Kabi Denmark
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ringer's acetate
D.3.9.1	CAS number	8026-10-6
D.3.9.3	Other descriptive name	RINGER'S SOLUTION
D.3.9.4	EV Substance Code	SUB33359
D.3.10	Strength
D.3.10.1	Concentration unit	mOsm/kg milliosmol(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	270
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Isotonic aqueous solution containing electrolytes

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with septic shock admitted to the intensive care unit

E.1.1.1

Medical condition in easily understood language

Overwhelming response to blood stream infection causing a life threatening drop in blood pressure necessitating admission to the intensive care unit.

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10040070
E.1.2	Term	Septic shock
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Efficacy of octaplasLG® administration as compared to crystalloids (standard) in patients with septic shock

E.2.2

Secondary objectives of the trial

Safety of octaplasLG® administration as compared to crystalloids (standard) in patients with septic shock

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria
1. Adult intensive care patients (age ≥18 years)
AND
2. Sepsis, defined as suspected or confirmed site of infection or positive blood culture and ≥2 of 4 systemic inflammatory response syndrome (SIRS) criteria fulfilled within the last 24h:
a) Temperature ≤ 36˚ C or ≥ 38˚C
b) Heart rate ≥ 90 beats per minute
c) Mechanical ventilation for acute respiratory process or respiratory rate ≥ 20 breaths per minute or PaCO2 < 4.2 kPa
d) WBC ≥ 12,000/mm³ OR ≤ 4,000/mm³ OR > 10% bands
AND
3. Septic shock requiring infusion of vasopressor/inotropic agents to maintain blood pressure

E.4

Principal exclusion criteria

Exclusion criteria
Patients are not eligible for inclusion in this trial if they fulfill one or more of the following criteria:
1. Documented refusal of blood transfusion OR
2. Treatment with GPIIb/IIIa inhibitors < 24h from screening OR
3. Withdrawal from active therapy OR
4. Previously within 30 days included in a randomised trial, if known at the time of enrolment OR
5. Known IgA deficiency with documented antibodies against IgA OR
6. 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
7. Known severe deficiencies of protein S OR
8. Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative urine-hCG) OR
9. Severe cirrhotic hepatic failure with expected need for treatment with terlipressin

E.5 End points

E.5.1

Primary end point(s)

Primary endpoints
• Change in microvascular perfusion from baseline to 6 hours after inclusion as evaluated by sidestream darkfield (SDF; MicroVision Medical, Amsterdam, The Netherlands) imaging technique.
• Change in biomarkers indicative of endothelial activation and damage (sE-selectin, syndecan-1, thrombomodulin, sVE-cadherin, nucleosomes) from baseline to 6 hours after inclusion

E.5.1.1

Timepoint(s) of evaluation of this end point

6 hours after inclusion in the trial as compared to baseline (inclusion)

E.5.2

Secondary end point(s)

Secondary endpoints
• Difference in 6 hours, 24 hours, 7, 30 and 90 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids)
• Length of stay in the ICU
• Days on vasopressors
• Days on ventilator
• Bleeding requiring > 2 RBC / day during the first 72 hours
• Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI during the first 72 hours.

Safety endpoints
• Maximal change in SOFA score from baseline to 6, 24, 48 and 72 hours as well as ICU day 7
• Acute Kidney Injury (AKI) according to RIFLE Criteria in the first 7 days
• Renal replacement therapy as deemed necessary by the attending physician during the first 30 days post-randomization.
• Thrombelastograph maximum amplitude (clot strength) in TEG and TEG Functional Fibrinogen (FF) at 6, 24, 48, 72 hours as compared to baseline
• Disseminated intravascular coagulation score (DIC) during the first 72 hours as well as day 7

E.5.2.1

Timepoint(s) of evaluation of this end point

Difference in 6 hours, 24 hours, 7, 30 and 90 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids)
Other secondary and safety endpoint during the first 72 hours and at 7 days

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS plus 6 month to allow for patient follow up and biomarker analyses

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Because septic shock is an acute life-threatening condition needing immediate intervention and resuscitation, always complicated with respiratory failure needing intubation and risk of cardiac arrest and death.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-04-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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