COVID19Phase 2COVIPLEXNCT04623255

Study of Plasma Exchange in Severe COVID-19

A Phase 2 study testing OCTAPLAS in people with COVID19, run by University College, London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: COVID19
What is being tested?: OCTAPLAS
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 23 participants
Where: 1 siteUnited Kingdom
Study dates: 16 Oct 2020to 31 Jan 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:
Raised LDH (> 2 x ULN)
Raised D Dimers (> 2X ULN)
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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

University College London Hospital
London, NW1 2PG

Other trials in United Kingdom

About this study

Official title: A Randomised Controlled Trial of Plasma Exchange With Standard of Care Compared to Standard of Care Alone in the Treatment of Severe COVID-19 Infection (COVIPLEX)

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.

Read the 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
Being tested: OCTAPLAS
Medical subject headings: COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OCTAPLASDrug
Also called plasma exchange
plasma exchange

Study groups in NCT04623255
Study group	Role	What they receive
STANDARD OF CARE	No intervention	Standard patient care for severe COVID-19
Plasma exchange	Active comparator	Standard patient care for severe COVID-19 with. plasma exchange daily for 5 days x 3 courses as required Receives: Drug: OCTAPLAS

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Inflammatory Marker Reduction of at Least 50% at Any Efficacy Time Point
The primary outcome in this study is a binary outcome indicating whether there was a reduction of at least 50% (compared to baseline) in two or more inflammatory markers [CRP, LDH, D-Dimer] during a"comparable duration of treatment" with either PEX or Standard of Care after study initiation.
Measured: The inflammatory markers recorded in this study are C reactive protein (CRP), lactate dehydrogenase(LDH) and D-Dimer, and we consider whether there is a reduction during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).
Change in Inflammatory Marker-CRP
To compare the change in inflammatory marker CRP with Plasma Exchange and control groups in patients with severe COVID-19.
Measured as number of participants who experienced a reduction of 50% at any follow-up time point.
Measured: We consider whether there is a reduction in inflammatory marker CRP during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).
Change in Inflammatory Marker-D Dimer
To compare the change in inflammatory marker D-dimer with Plasma Exchange and control groups in patients with severe COVID-19.
Measured as number of participants who experienced a reduction of 50% at any follow-up time point.
Measured: We consider whether there is a reduction in inflammatory marker D-dimer during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).
Change in Inflammatory Marker-LDH
To compare the change in inflammatory marker LDH with Plasma Exchange and control groups in patients with severe COVID-19.
Measured as number of participants who experienced a reduction of 50% at any follow-up time point.
Measured: We consider whether there is a reduction in inflammatory marker LDH during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Oct 202031 Jan 2022

First posted10 Nov 2020
Study start16 Oct 2020
Primary completion31 Jan 2022
Study completion31 Jan 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for COVID19Studies of the same condition, open and under way.
More trials run by University College, LondonThe 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04623255
Sponsor's protocol ID: 132796
Acronym: COVIPLEX
Status last verified: May 2024
First submitted: 11 Jun 2020
Last updated: 7 Jun 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 39043682

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 7 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised Controlled Trial of Plasma Exchange With Standard of Care Compared to Standard of Care Alone in the Treatment of Severe COVID-19 Infection (COVIPLEX)
ClinicalTrials.gov ID: NCT04623255
Acronym / sponsor ID: COVIPLEX / 132796
Conditions: COVID19
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: University College, LondonUniversity, hospital or other
Study start: 16 Oct 2020 (actual)
Primary completion: 31 Jan 2022 (actual)
Study completion: 31 Jan 2022 (actual)
First posted: 10 Nov 2020 (actual)
Results: Posted 7 Jun 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
STANDARD OF CARE	No intervention	–Standard patient care for severe COVID-19
Plasma exchange	Active comparator	Drug: OCTAPLASStandard patient care for severe COVID-19 with. plasma exchange daily for 5 days x 3 courses as required

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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:
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

Key exclusion criteria (5 listed)

Significant co-morbid illness with treatment escalation limited to CPAP

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
OCTAPLASAlso: plasma exchangeplasma exchange	Drug	Plasma exchange

Primary outcome

Number of Participants With Inflammatory Marker Reduction of at Least 50% at Any Efficacy Time Point
Time frame: The inflammatory markers recorded in this study are C reactive protein (CRP), lactate dehydrogenase(LDH) and D-Dimer, and we consider whether there is a reduction during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).
The primary outcome in this study is a binary outcome indicating whether there was a reduction of at least 50% (compared to baseline) in two or more inflammatory markers [CRP, LDH, D-Dimer] during a"comparable duration of treatment" with either PEX or Standard of Care after study initiation.
Change in Inflammatory Marker-CRP
Time frame: We consider whether there is a reduction in inflammatory marker CRP during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).
To compare the change in inflammatory marker CRP with Plasma Exchange and control groups in patients with severe COVID-19. Measured as number of participants who experienced a reduction of 50% at any follow-up time point.
Change in Inflammatory Marker-D Dimer
Time frame: We consider whether there is a reduction in inflammatory marker D-dimer during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).
To compare the change in inflammatory marker D-dimer with Plasma Exchange and control groups in patients with severe COVID-19. Measured as number of participants who experienced a reduction of 50% at any follow-up time point.
Change in Inflammatory Marker-LDH
Time frame: We consider whether there is a reduction in inflammatory marker LDH during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).
To compare the change in inflammatory marker LDH with Plasma Exchange and control groups in patients with severe COVID-19. Measured as number of participants who experienced a reduction of 50% at any follow-up time point.

Results and safety

Results posted to the registry on 7 Jun 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
STANDARD OF CARE	11	11
Plasma Exchange	12	11

Primary outcome: Number of Participants With Inflammatory Marker Reduction of at Least 50% at Any Efficacy Time Point

Time frame: The inflammatory markers recorded in this study are C reactive protein (CRP), lactate dehydrogenase(LDH) and D-Dimer, and we consider whether there is a reduction during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).. Count of participants. Unit: Participants

Measure	STANDARD OF CARE n = 10	Plasma Exchange n = 10
Value	5	8

STANDARD OF CARE vs Plasma Exchange: p = 0.16, Chi-squared

Population analysed: Note: 23 patients with severe COVID-19 were randomised. One patient withdrew from the study 1 day after randomisation and their data has been excluded from the analysis. There were no follow-up data for a further two participants for this endpoint (1 from each arm) and hence they were omitted from this analysis, so data from a total of 20 participants was analysed.

Primary outcome: Change in Inflammatory Marker-CRP

Time frame: We consider whether there is a reduction in inflammatory marker CRP during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).. Count of participants. Unit: Participants

Measure	STANDARD OF CARE n = 10	Plasma Exchange n = 10
Value	8	7

STANDARD OF CARE vs Plasma Exchange: p = 0.606, Chi-squared

Primary outcome: Change in Inflammatory Marker-D Dimer

Time frame: We consider whether there is a reduction in inflammatory marker D-dimer during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).. Count of participants. Unit: Participants

Measure	STANDARD OF CARE n = 10	Plasma Exchange n = 9
Value	4	6

STANDARD OF CARE vs Plasma Exchange: p = 0.245, Chi-squared

Population analysed: Note: 23 patients with severe COVID-19 were randomised. One patient withdrew from the study 1 day after randomisation and their data has been excluded from the analysis. There were no follow-up data for a further three participants for this endpoint (1 from standard of care arm and 2 from plasma exchange arm) and hence they were omitted from this analysis, so data from a total of 19 participants was analysed.

Primary outcome: Change in Inflammatory Marker-LDH

Time frame: We consider whether there is a reduction in inflammatory marker LDH during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).. Count of participants. Unit: Participants

Measure	STANDARD OF CARE n = 10	Plasma Exchange n = 10
Value	5	6

STANDARD OF CARE vs Plasma Exchange: p = 0.653, Chi-squared

Adverse events

Time frame: All adverse events will be recorded from consent to the end of trial (day 28 after randomisation).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
STANDARD OF CARE	4 of 11 (36.4%)	11 of 11 (100%)	1 of 11
Plasma Exchange	6 of 11 (54.5%)	10 of 11 (90.9%)	2 of 11

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39043682Arulkumaran 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.
Individual participant dataSharing planned: No

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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.

Marie Scully, MD principal investigator

University College London Hospitals

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing OCTAPLAS in people with COVID19, run by University College, London at 1 site in United Kingdom.

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 8 inclusion and 5 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: finished, as of the sponsor's last update on 7 Jun 2024. 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 United Kingdom. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Inflammatory Marker Reduction of at Least 50% at Any Efficacy Time Point (time frame: The inflammatory markers recorded in this study are C reactive protein (CRP), lactate dehydrogenase(LDH) and D-Dimer, and we consider whether there is a reduction during the designated follow-up period (i.e. follow-up days 6, 7, 14, 21 and 28).). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04623255, which also lists 1 linked publication.

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 7 Jun 2024.