Early Use of Hyperimmune Plasma in COVID-19 (COV-II-PLA)

COVID-19 Wave II Study for Assessing the Early Use of Hyperimmune Plasma for the Treatment of COVID-19 Patients Needing Non-invasive or Invasive Mechanical Ventilation

The study assesses the efficacy of early administration of hyperimmune plasma in covid-19 patients who are on CPAP or intubated. Efficacy is measured as a 2 point decrease in the WHO scale

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19
• Intervention / Treatment: Other: hyperimmune plasma

Detailed Description

Patients who satisfy eligibility criteria and in particular have started positive pressure respiratory support not more than no more than 48 hours are administered 200 to 300 ml in 2 or 3 times administered over a time window of 5 days. . Plasma titration will depend on the availability in the local Plasma Bank; any titre ≥ 1:80 will be acceptable. primary endpoint will be assessed at 28 days; vital status will be further investigated at 3 and 6 months.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Catherine Klersy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent prior to performing study procedures. Witnessed oral consent will be accepted in order to avoid paper handling. Written consent by patient or representatives will be obtained as soon as possible.
2. Male or female adult patient ≥18 years of age at time of enrolment.
3. Laboratory-confirmed SARS-CoV-2 infection as determined by real-time RT-PCR in naso/oropharyngeal swabs or any other relevant specimen..
4. Patient is hospitalized for COVID-19, is severely hypoxic with a P/F ≤ 200 while breathing room air or supplemental oxygen and requires positive pressure respiratory support, either non-invasive (helmet/mask CPAP or NIV) or invasive (endotracheal intubation and mechanical ventilation)
5. No more than 48 hours between the onset of positive pressure respiratory support and treatment administration day
6. Evidence of pulmonary infiltrates at chest imaging (chest x-ray, CT scan or LUS)
7. The patient is not eligible in the Tsunami trial.

Exclusion Criteria:

1. Participation in any other clinical trial of an experimental treatment for COVID-19.
2. In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments.
3. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30).
4. Pregnancy
5. Current documented and uncontrolled bacterial infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single; hyperimmune plasma with titre 1:80 or more	Other: hyperimmune plasma; plasma collected from convalescent Covid-19 donors with titre 1:80 or more

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical improvement (efficacy)	Clinical improvement is obtained when a patient decreases his/her score by 2 points on the ten-category ordinal WHO scale or is discharged alive from the hospital, whichever comes first. The WHO scale is chosen in accordance with the "Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme" recently published in Lancet Infectious Diseases (WHO, 2020).	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ventilation	Ventilator-free days	Days: from 0 to 7, 14 and 28
WHO (World Health Organization) scale	WHO scale score reached. Minimum score is 0: unifected (no viral RNA detected); maximum score 10 (dead)	From day 0 to 28 days
SOFA (Sequential Organ Failure Assessment) score	Sequential Organ Failure Assessment Score (SOFA score). This score is used to determine the extent of a person's organ function or rate of failure, from 0 to 24, with severity increasing with higher the scores	Days: from 0 to 7, 14 and 28
naso-pharyngeal swab	Time to a negative SARS-COV2 naso-pharyngeal swab for upper respiratory tract or BAL/BRASP for lower respiratory	Days: from 0 to 7, 14 and 28
SARS-CoV2	Log10 change in SARS-CoV2	28 days
P/F	P/F ratio. P/F is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage)	Days: from 0 to 7, 14 and 28
thrombosis	Occurrence of deep vein thrombosis or pulmonary embolism assessed using the most appropriate imaging approach	Days: from 0 to 7, 14 and 28
curarization	Total duration of mechanical ventilation, ventilatory weaning and curarisation in days	Days: from 0 to 7, 14 and 28
complication kidney	KDIGO score Kidney Disease: Improving Global Outcomes (KDIGO)	Days: from 0 to 7, 14 and 28
complication lung	Occurrence of ventilator-acquired pneumonia - Radiological and clinical context associated with a bacteriological sampling in culture of tracheal secretions, bronchiolar-alveolar lavage or a protected distal sampling	Days: from 0 to 7, 14 and 28
Leucocytes	Biological efficacy endpoints: Leucocytes (x10^3/ul)	Days: from 0 to 7, 14 and 28
Lymphocytes	Biological efficacy endpoints: Lymphocytes (x10^3/ul)	Days: from 0 to 7, 14 and 28
C-reactive protein	Biological efficacy endpoints: C-reactive protein (mg/dL)	Days: from 0 to 7, 14 and 28
D-dimer	Biological efficacy endpoints: D-dimer (ug/L)	Days: from 0 to 7, 14 and 28
Troponin I (TnI)	Biological efficacy endpoints: TNI (ng/L)	Days: from 0 to 7, 14 and 28
PCTI (Procalcitonin) (ng/mL)	Biological efficacy endpoints: PCTI (Procalcitonin) (ng/mL)	Days: from 0 to 7, 14 and 28
Ferritin	Biological efficacy endpoints: Ferritin (ng/ml)	Days: from 0 to 7, 14 and 28
Albumin	Biological efficacy endpoints: Albumin (mg/dL)	Days: from 0 to 7, 14 and 28
LDH	Biological efficacy endpoints: LDH (mU/mL)	Days: from 0 to 7, 14 and 28
Lung Ultrasound Score (LUS)	Total Lung Ultrasound Score S score	Days: from 0 to 7, 14 , 28 and 6 months
ecmo	Occurrence of ECMO implant	28 days
death	All cause mortality	28 days, 3 and 6 months
hospitalization	days total hospitalization and of ICU hospitalization	28 days
Lung Function tests	Lung Function tests	6 months
High resolution computed tomography (HRCT)	HRCT findings of the thorax	6 months
Improvement mortality	rate of clinical improvement and mortality between the patients in the study and the cohort enrolled in the local SMACORE registry	28 days

Collaborators and Investigators

• Sponsor: Catherine Klersy
• Collaborators: Fondazione IRCCS Policlinico San Matteo di Pavia
• Investigators: Principal Investigator: Francesco Mojoli, MD, Fondazione IRCCS Policlinico San Matteo

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2020
• Primary Completion (Actual): May 19, 2021
• Study Completion (Anticipated): May 19, 2022

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 21, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: hyperimmune plasma; positive pressure respiratory support
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 100490/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: may be available upon motivated requesto to PI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No