Study of Plasma Exchange in Severe COVID-19

NCT ID: NCT04623255

Last Updated: 2024-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-16
• Study Completion Date: 2022-01-31

Brief Summary

The rationale in severe COVID19 infection is to undertake PEX to aid reduction of the hyperinflammation and reduce the morbidity and mortality to the lungs, but also systemically, such as the heart, kidneys and brain. A feasibility study of PEX therapy has been undertaken and confirmed a reduction in the inflammatory markers, no VTE/arterial events and normalisation of the renal function and cardiac function throughout the period of therapy. As plasma exchange is an intensive treatment modality, blocks of 5 daily PEX will be undertaken. Further blocks of PEX treatment can be initiated as dictated by the clinical and laboratory parameters. Unlike many therapeutic schedules, there is no immunosuppression associated with PEX; indeed, the resulting decrease in inflammatory markers were shown to be associated with an increase and sustained lymphocytes count.

Detailed Description

COVID19 is a viral pandemic associated with primarily respiratory pathology, in the form of microvascular and macrovascular thrombosis. In patients requiring hospital admission, there is severe disease, requiring respiratory support, from high dose oxygen therapy or ventilatory assistance, which may be invasive or non invasive. The pathology of COVID19 is poorly understood, but it is accepted there is an inflammatory-thrombotic basis. Despite current therapeutic platforms, there is no consensus on a specific therapy within a trial setting that has proven benefit in severe COVID 19.

Thrombotic microangiopathies, such as TTP, are a different disease, but have a comparable prothrombotic phenotype, and similar or higher inflammatory parameters, including D Dimers, ferritin, LDH and IL-6 at acute presentation and resolve with plasma exchange (PEX). The rationale in severe COVID19 infection is to undertake PEX to aid reduction of the hyperinflammation and reduce the morbidity and mortality to the lungs, but also systemically, such as the heart, kidneys and brain. A feasibility study of PEX therapy has been undertaken and confirmed a reduction in the inflammatory markers, no VTE/arterial events and normalisation of the renal function and cardiac function throughout the period of therapy. As plasma exchange is an intensive treatment modality, blocks of 5 daily PEX will be undertaken. Further blocks of PEX treatment can be initiated as dictated by the clinical and laboratory parameters. Unlike many therapeutic schedules, there is no immunosuppression associated with PEX; indeed, the resulting decrease in inflammatory markers were shown to be associated with an increase and sustained lymphocytes count. Therefore, as patients with COVID-19 have elevated procoagulant factors including VWF and factor VIII secondary to direct endothelial activation. This is associated with an exaggerated pro-inflammatory immune response and microvascular thrombosis; resulting in multi-organ dysfunction and eventually death. PEX will improve coagulopathy, as measured by VWF:ADAMTS 13 ratio and D Dimers, with an associated reduction in inflammation, organ-related microthrombosis, and ventilatory support.

Conditions

COVID19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

STANDARD OF CARE

Standard patient care for severe COVID-19

Group Type: NO_INTERVENTION

No interventions assigned to this group

Plasma exchange

Standard patient care for severe COVID-19 with. plasma exchange daily for 5 days x 3 courses as required

Group Type: ACTIVE_COMPARATOR

OCTAPLAS

Intervention Type: DRUG

plasma exchange

Interventions

OCTAPLAS

plasma exchange

Intervention Type: DRUG

Other Intervention Names

plasma exchange

Eligibility Criteria

Inclusion Criteria

• Age 18-70
• Proven COVID-19/high clinical suspicion of COVID-19
• Hypoxia/respiratory compromise defined as requiring respiratory support of >2L/min of oxygen by nasal cannulae to maintain SpO2<96%.
• Raised inflammatory parameters: at least 2 of the following:

1. Raised LDH (> 2 x ULN)

2. Raised D Dimers (> 2X ULN)

3. Raised CRP (>2X ULN)

• Females of childbearing potential have a negative pregnancy test within 7 days prior to being randomised. Participants are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal

Exclusion Criteria

• Significant co-morbid illness with treatment escalation limited to CPAP

• Active bleeding
• PF ratio < 100 on mechanical ventilation OR noradrenaline requirement > 0.5mcg/kg/min to maintain MAP > 65mmHg (suggests futility)
• Known allergies to Octaplas or excipients
• Females who are pregnant

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie Scully, MD

Role: PRINCIPAL_INVESTIGATOR

UCLH

Locations

University College London Hospital

London, , United Kingdom

Countries

United Kingdom

References

Arulkumaran N, Thomas M, Stubbs M, Prasanna N, Subhan M, Singh D, Ambler G, Waller A, Singer M, Brealey D, Scully M. A randomised controlled trial of plasma exchange compared to standard of care in the treatment of severe COVID-19 infection (COVIPLEX). Sci Rep. 2024 Jul 23;14(1):16876. doi: 10.1038/s41598-024-67028-3.

Reference Type: DERIVED

PMID: 39043682 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

132796

Identifier Type: -

Identifier Source: org_study_id