Plasmaexchange in Early Septic Shock

NCT ID: NCT03065751

Last Updated: 2019-08-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2021-07-31

Brief Summary

Sepsis is defined by the occurrence of a systemic inflammatory response syndrome (SIRS) in the context of infection. Unfortunately, its incidence appears to be rising, and the mortality of septic shock remains extraordinary high (> 60%). Death in sepsis arises from shock and multi organ dysfunction that are - at least in part - triggered by an inadequate response of the host's immune system to the infection. Given the injurious role of 1) this overwhelming immune response and 2) the consumption of protective plasmatic factors (e.g. vWF cleaving proteases, hemostatic factors etc.) while the disease is progressing the investigators hypothesize that early therapeutic plasma exchange (TPE) in the most severely ill individuals might improve hemodynamics, oxygenation and ultimately survival. This therapeutic strategy combines 2 major aspects in 1 procedure: 1. removal of harmful circulating molecules and 2. replacement of protective plasma proteins. The investigators designed the EXCHANGE trial to analyze in a randomized fashion the benefit of TPE as an add-on treatment to state of the art standard sepsis care. Only patients with early septic shock (< 12 hrs) and high catecholamine doses (noradrenaline > 0.4 ug/kg bodyweight/min) will be included. Those in the treatment group will receive 3 TPEs within three consecutive days. The primary outcome is 28-day all cause mortality. To show an assumed reduction from 60% to 45% in the experimental group, a sample size of 173 patients per group has been calculated. The overall sample size is therefore n=346. The recruitment period is 3 years (+3 months observation) and will be performed in 11 national centers in Germany. Secondary endpoints (including hemodynamics, oxygenation, coagulation, and microcirculation) will be assessed on day 1, 2, 3 before and after TPE and on day 4, 5, 7 and 14.

Project management and data monitoring will be organized by the Hanover Clinical Trial Center and biostatistics including a web-based randomization will be performed by the Institute of biometrics (Prof. Koch) at Hannover Medical School.

The investigators hope to demonstrate a potential benefit of an additive treatment approach to improve the outcome of patients suffering from an under-recognized but deadly disease.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

TPE

Group Type: ACTIVE_COMPARATOR

Plasmaexchange

Intervention Type: DEVICE

TPE against fresh frozen plasma

Kontroll

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Plasmaexchange

TPE against fresh frozen plasma

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Onset of septic shock within less than 12 hrs
• Noradrenaline dose of ≥ 0.4 ug/kg/min bodyweight (target MAD ≥ 65 mmHg) ≥ 30 min

Exclusion Criteria

• Age<18 years and > 80 years
• Pregnancy
• Known history of transfusion reactions

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hannover Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hannover Medical School

Hanover, Lower Saxony, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Sascha David, MD

Role: CONTACT

david.sascha@mh-hannover.de

0049 511532 ext. 9357

Haller Hermann, MD

Role: CONTACT

nephrologie@mh-hannover.de

0049 511532 ext. 6319

Facility Contacts

Sascha David, MD

Role: primary

david.sascha@mh-hannover.de

0049 511532 ext. 9357

References

Stahl K, Schmidt JJ, Seeliger B, Schmidt BMW, Welte T, Haller H, Hoeper MM, Budde U, Bode C, David S. Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock. Crit Care. 2020 Mar 2;24(1):71. doi: 10.1186/s13054-020-2799-5.

Reference Type: DERIVED

PMID: 32122366 (View on PubMed)

Knaup H, Stahl K, Schmidt BMW, Idowu TO, Busch M, Wiesner O, Welte T, Haller H, Kielstein JT, Hoeper MM, David S. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers. Crit Care. 2018 Oct 30;22(1):285. doi: 10.1186/s13054-018-2220-9.

Reference Type: DERIVED

PMID: 30373638 (View on PubMed)

Other Identifiers

2786-2015

Identifier Type: -

Identifier Source: org_study_id