Vasculopathic Injury and Plasma as Endothelial Rescue in Septic Shock (SHOCK) Trial

Phase 2

Completed

• Conditions: Septic Shock
• Interventions: Drug: OctaplasLG; Drug: Ringer-Acetate

• Registration Number: NCT03092245
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

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

This is a single center, randomized (1:1, active : standard of care), controlled, open-label, investigator-initiated pilot phase IIa trial in patients with septic shock investigating the efficacy and safety of administrating OctaplasLG® as compared to crystalloids, such as Ringer-Acetate (standard of care) in a total of 40 patients.

40 patients will be enrolled:

* Patients in the active treatment group (n = 20 patients) will receive OctaplasLG® as volume support according to trial algorithm.

* Patients in the standard of care group (n = 20 patients) will receive crystalloids, such as Ringer-Acetate, as volume support according to trial algorithm.

All patients will be treated according to the standard ICU care.

Study Timeline

• Study First Submitted: 2017-02-21
• Study First Submitted QC: 2017-03-21
• Study First Posted: 2017-03-27
• Study Start: 2017-04-18
• Primary Completion: 2019-04-17
• Study Completion: 2019-04-17
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-18
• Last Update Posted: 2023-01-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1. Adult intensive care patients (age ≥ 18 years) AND

2. Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection AND

3. Quick SOFA (qSOFA) with two or more of

   1. Respiratory rate ≥ 22/min
   2. Altered mentation (Glasgow Coma Scale score < 15)
   3. Systolic blood pressure ≤ 100mmHg AND

4. Septic shock, defined as a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L despite adequate volume resuscitation AND

5. Requiring infusion of noradrenalin 0.10 mcg/kg/min or more to maintain blood pressure AND

6. Respiratory failure requiring intubation and mechanical ventilation

Exclusion 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 an interventional trial 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
OctaplasLG	OctaplasLG	OctaplasLG® is an industrial donor plasma product pooled from 630 -1520 single donor units. It possesses unique features when compared to standard FFP, such as having a standardized concentration of natural pro- and anti-coagulation factors, a standardized volume as well as being pathogen-free.12 Most importantly, the manufacturing method of OctaplasLG® removes immune complexes and cells in several steps of microfiltration. The manufacturing process also inactivates viral, bacterial and prion pathogen by immune neutralization, solvent-detergent treatment and a prion specific ligand affinity chromatography step.
Ringer-Acetate	Ringer-Acetate	standard of care resuscitation fluid Ringer-acetate is a mixture of electrolytes in water to a slightly hypotonic solution.

Primary Outcome Measures

Name	Time	Method
Microscan at 24 hours	24 hours after baseline	Change in microvascular perfusion from baseline to 24 hours after inclusion as evaluated by sidestream darkfield (SDF; MicroVision Medical, Amsterdam, The Netherlands) imaging technique.
Biomarkers at 24 hours	24 hours after baseline	Change in biomarkers indicative of endothelial activation and damage (sE-selectin, syndecan-1, thrombomodulin, VEGFR1, VEGF, nucleosomes) from baseline to 24 hours after inclusion.

Secondary Outcome Measures

Name	Time	Method
24 hour mortality	24 hours after inclusion	Difference in 24 hours mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).
Days on vasopressors	Days, assessed at 30-days and 90-days	The number of days on vasopressors after inclusion
Days on ventilator	Days, assessed at 30-days and 90-days	The number of days on vasopressors after inclusion
Transfusion requirements	For the first 7 days after inclusion	Bleeding requiring \> 2 RBC / day
7 day mortality	7 days after inclusion	Difference in 7 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).
Renal Replacement Therapy	For the first 7 days after inclusion	recording whether the patient is receiving dialysis or not
30 day mortality	30 days after inclusion	Difference in 30 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).
Length of stay in the ICU	Days, assessed at 30-days and 90-days	The number of days in the ICU after inclusion
90 day mortality	90 days after inclusion	Difference in 90 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).
Serious Adverse Reactions at 72 hours	For the first 72 hours after inclusion	Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI
Serious Adverse Reactions at day 30	At day 30 after inclusion	Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI
Oxygenation	At 24 hours, 48 hours, 72 hours and at day 7 after baseline	As evaluated by the PaO2/FiO2-ratio during the ICU stay
RIFLE criteria: Risk, Injury, and Failure, Loss and End-stage kidney disease	For the first 7 days in the ICU	Acute Kidney Injury according to RIFLE criteria

Trial Locations

Locations (1)

ICU Bispebjerg Hospital; 🇩🇰 Copenhagen, Denmark