Combined Use of Immunoglobulin and Pulse Steroid Therapies in Severe Covid-19 Patients

Evaluation of the Retrospective Clinical Results of the Combined Use of Immunoglobulin and Pulse Steroid Therapies in Severe Covid-19 Patients Followed in Intensive Care Unit

In December 2019, SARS-COV-2 was isolated from patients for the first time . It then rapidly turned into a pandemic affecting the whole world.While most Covid patients survive the disease with mild symptoms, some may develop severe organ failure and respiratory failure requiring mechanical ventilation. COVİD-19 pneumonia may progress into acute respiratory distress syndrome (ARDS). The most important reason for this has been shown in studies; is thought to be because a group of patients develop a cytokine storm-associated hyperinflammatory state characterized by features of macrophage activation syndrome (MAS). The aim of this study was to evaluate the clinical outcomes of the combined use of pulse steroid and intravenous immunoglobulin therapy in patients with severe COVID-19 with severe respiratory distress in intensive care unit.

Study Overview

• Status: Completed
• Conditions: Pulse Steroid and Immunoglobulins Drugs in Covid 19 Patients
• Intervention / Treatment: Drug: pulse steroid and nanogam

Detailed Description

In December 2019, SARS-COV-2 was isolated from patients for the first time . It then rapidly turned into a pandemic affecting the whole world.While most Covid patients survive the disease with mild symptoms, some may develop severe organ failure and respiratory failure requiring mechanical ventilation . COVİD-19 pneumonia may progress into acute respiratory distress syndrome (ARDS) , diffuse alveolar damage, and vascular endothelitis, which is comlicated with trombosis and hemorrhage. .

The most important reason for this has been shown in studies; is thought to be because a group of patients develop a cytokine storm-associated hyperinflammatory state characterized by features of macrophage activation syndrome (MAS), such as lymphopenia, elevated ferritin and elevated d-dimer. Increased proinflammatory cytokine release, especially as a result of stimulation of the immune system, has been shown to be associated with this hyperinflammatory phase .

The immune system triggered by viral infections is essential for fighting pathogens. However, the excessive production of pro-inflammatory cytokines caused by SARS-COV-2 can cause tissue damage that can lead to fatal acute respiratory distress .

Therefore, aiming to suppress the cytokine storm seems to be of critical importance for COVID-19 and similar respiratory infections that cause acute respiratory distress . Many agents have been used for this purpose, but there is no clear evidence for the management and treatment of cytokine storm.

Immunosuppression plays an important role in the treatment of cytokine storm. Studies have reported positive results of steroids used for this purpose in elderly COVID-19 patients . Various immunomodulatory agents have also been used for this purpose. In addition to treatments targeting a specific molecule such as IL-6, IL-1, agents that affect various branches of the immune inflammatory system such as intravenous immunoglobulin can be used .

The aim of this study was to evaluate the clinical outcomes of the combined use of pulse steroid and intravenous immunoglobulin therapy in patients with severe COVID-19 with severe respiratory distress in intensive care unit.

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey
  • Konya, Turkey, 42020
    • Konya City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients with 2019-ncov infection confirmed by PCR;
• Absolute value of lymphocytes < 0. 6x 109/L;
• Brescia-COVID respiratory severity scale (BCRSS) score ≥3
• Hyperinflammation (defined as elevation of C-reactive protein (CRP) ≥50 mg/L or ferritin ≥500 ng/ ml)
• Severe respiratory failure within 48 hours and requires admission to ICU. (severe respiratory failure was defined as PaO2/FiO2 < 300 mmHg and was supported by positive pressure mechanical ventilation (including non-invasive and invasive mechanical ventilation, PEEP>=5cmH2O))

Exclusion Criteria:

• Age < 18
• Pregnant
• Allergic to experimental drugs
• The underlying disease is very serious and the expected survival time is less than 6 months (such as advanced malignant tumor);
• COPD or end-stage lung disease requires home oxygen therapy
• Expected survival time not exceeding 48 hours
• Autoimmune diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: the group receiving standard treatment; In the group receiving standard treatment, hydroxychloroquine (400 mg/day for 5 days), low moleculer weight heparin, acetylsalicylic acid, favipiravir (3200 mg on day 1, 1200 mg on days 2-5).	Drug: pulse steroid and nanogam; patients received pulse steroid and ivig treatments in addition to standard treatment.
Active Comparator: the group receiving IVIG and pulse steroid; In the IVIG and pulse steroid group, patients received pulse steroid (250 mg/day methylprednisolone for 5 days) and intravenous immunoglobulin (400 mg/kg/day for 5 days) in addition to standard treatment. The IVIG preparations given to the patients were in 100 ml volume and 10% concentration, and the commercial name was Nanogam.	Drug: pulse steroid and nanogam; patients received pulse steroid and ivig treatments in addition to standard treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
all cause mortality rate	died at day 28	28 days
ventilation free days		28 days
ICU free days		28 days
absolute lymphocyte , white blood cell , neutrophil , ferritin , dimer , crp counts	counts on the first day of hospitalization, in the middle and at discharge from intensive care	on the first day of hospitalization, in the middle and at discharge from intensive care
SOFA score	SOFA score at Day 1, with scores range from 0 to 24 and higher score means worse outcome	Day 1
invasive and non-invasive respiratory support	intubated	28 days
vasopressor support	vasopressor support needs	28 days
renal replacement therapy	renal replacement therapy needs	28 days

Collaborators and Investigators

• Sponsor: Konya City Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2020
• Primary Completion (Actual): November 14, 2020
• Study Completion (Actual): November 14, 2020

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• 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: konya city hospital,konya

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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