Plasma Exchange in Patients With COVID-19 Disease and Invasive Mechanical Ventilation: a Randomized Controlled Trial

NCT ID: NCT04374539

Last Updated: 2022-04-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-29
• Study Completion Date: 2021-06-29

Brief Summary

Plasma exchanges with 5% human albumin (2/3 of the exchanged plasma volume) and fresh frozen plasma (FFP: 1/3) in patients with quick <50% or only with 5% albumin in patients with quick of 50% or more. We will exchange between 1.2 and 1.5 plasma volumes, that will vary according to sex, weight, height and hematocrit.

Detailed Description

Plasma exchange (PE) is a standardized and safe therapeutic procedure, used in the treatment of various diseases that require rapid and prolonged elimination of endogenous and exogenous substances, with deleterious effects on the function of different organs and systems. The efficacy and safety of PE has been demonstrated in patients with fulminant hepatitis (FH), an entity characterized by an exacerbated inflammatory response, multi-organ failure, and high short-term mortality. In FH, plasma exchange improves systemic inflammation, prevents organ failure and renal support requirements, and improves survival. Such treatment eliminates important endogenous and exogenous inducers of the systemic inflammatory response (PAMPs and DAMPs), proinflammatory mediators (cytokines and ROS), and other biologically active substances (nitric oxide, prostaglandins, and bradykinin) that are involved in the pathogenesis of organ failure. Several case reports also suggest that PE is an effective rescue therapy in critically ill patients with influenza A (H1N1). However, the efficacy of PE has not been evaluated in critically ill patients with COVID-19 disease.

Conditions

Coronavirus

Study Design

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

Study Groups

Plasma exchange

Plasma exchange with human serum albumin + Polyclonal immunoglobulin + standard medical treatment

Group Type: EXPERIMENTAL

Plasma exchange

Intervention Type: BIOLOGICAL

Plasma exchanges with 5% human albumin and fresh frozen plasma in patients with quick <50% or only with 5% albumin in patients with quick of 50% or more. We will exchange between 1.2 and 1.5 plasma volumes, that will vary according to sex, weight, height and hematocrit.

Polyclonal immunoglobulin will be administered at a dose of 100 mg / kg ev after each plasma exchange.

Standar Medical treatment Kaletra:

lopinavir/ritonavir: 2c/12h 7 days

• Hydroxychloroquine sulfate 400 mg/12h the first day followed by 200 mg /12h 4 days
• Azithromycin 500 mg first day, followed by 250 mg /d 4 days (oral or EV)
• Tocilizumab 400 mg (weight <75Kgs) or 600 mg (weight ≥ 75 Kg)
• Methylprednisolone 250 mg EV three days and 30 mg/d another 3 days
• Anakinra 200mg/ 12h SBC first day, 200mg / 24h SBC two more days
• Clexane 40-60 mg/d

Standar medical treatment

Standar medical treatment

Group Type: ACTIVE_COMPARATOR

Standar medical treatmen

Intervention Type: DRUG

Kaletra: lopinavir/ritonavir: 2c/12h 7 days

• Hydroxychloroquine sulfate 400 mg/12h the first day followed by 200 mg /12h 4 days
• Azithromycin 500 mg first day, followed by 250 mg /d 4 days (oral or EV)
• Tocilizumab 400 mg (weight <75Kgs) or 600 mg (weight ≥ 75 Kg)
• Methylprednisolone 250 mg EV three days and 30 mg/d another 3 days
• Anakinra 200mg/ 12h SBC first day, 200mg / 24h SBC two more days
• Clexane 40-60 mg/d

Interventions

Plasma exchange

Plasma exchanges with 5% human albumin and fresh frozen plasma in patients with quick <50% or only with 5% albumin in patients with quick of 50% or more. We will exchange between 1.2 and 1.5 plasma volumes, that will vary according to sex, weight, height and hematocrit.

Polyclonal immunoglobulin will be administered at a dose of 100 mg / kg ev after each plasma exchange.

Standar Medical treatment Kaletra:

lopinavir/ritonavir: 2c/12h 7 days

• Hydroxychloroquine sulfate 400 mg/12h the first day followed by 200 mg /12h 4 days
• Azithromycin 500 mg first day, followed by 250 mg /d 4 days (oral or EV)
• Tocilizumab 400 mg (weight <75Kgs) or 600 mg (weight ≥ 75 Kg)
• Methylprednisolone 250 mg EV three days and 30 mg/d another 3 days
• Anakinra 200mg/ 12h SBC first day, 200mg / 24h SBC two more days
• Clexane 40-60 mg/d

Intervention Type: BIOLOGICAL

Standar medical treatmen

Kaletra: lopinavir/ritonavir: 2c/12h 7 days

• Hydroxychloroquine sulfate 400 mg/12h the first day followed by 200 mg /12h 4 days
• Azithromycin 500 mg first day, followed by 250 mg /d 4 days (oral or EV)
• Tocilizumab 400 mg (weight <75Kgs) or 600 mg (weight ≥ 75 Kg)
• Methylprednisolone 250 mg EV three days and 30 mg/d another 3 days
• Anakinra 200mg/ 12h SBC first day, 200mg / 24h SBC two more days
• Clexane 40-60 mg/d

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female subject ≥18 years and < 80 years of age;

2. Subjects with diagnosis of COVID-19 disease by PCR in nasopharyngeal smear, sputum, or bronchial aspirates;

3. Subjects admitted in ICU with invasive mechanical ventilation;

4. Informed consent granted via telephone by relatives or legal representative

Exclusion Criteria

1. More than seven days with invasive mechanical ventilation

2. Refractory Shock (Noradrenaline dose > 0.5 micrograms/ kg/minute)

3. Decompensated Cirrhosis

4. Chronic kidney disease requiring hemodialysis

5. Active neoplastic disease

6. Severe chronic heart failure (NYHA class III or IV)

7. Severe pulmonary disease (GOLD III or IV)

8. HIV infection (AIDS criteria)

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

Sponsors

Fundacion Clinic per a la Recerca Biomédica

OTHER

Sponsor Role: lead

Responsible Party

Anna Cruceta

Project Manager

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Countries

Spain

Other Identifiers

2020-001722-66

Identifier Type: -

Identifier Source: org_study_id