STS Administration on Coronavirus Disease (COVID-19) Patients in Critical Care

NCT ID: NCT05277285

Last Updated: 2023-01-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2023-12-31

Brief Summary

The primary purpose is to describe the safety of administration of three doses of STS to critically ill patients with confirmed COVID-19. A secondary purpose is to describe data on the clinical efficacy of administration of up to three doses of STS in critically ill patients with confirmed COVID-19.

Detailed Description

With the appearance of the COVID-19 pandemic, a race for the discovery of effective treatments to combat SARS-CoV-2 infection and its sequelae commenced. Some patients with COVID-19 develop severe acute respiratory syndrome which is the main reason for death. The aim of this study is to spearhead pharmacotherapeutic solutions for COVID-19 patients in the intensive care which have proven to be the hardest to treat due to the high death rate, the long-term allocation of patients in ICU, and the slow recovery that oftentimes leads to residual symptoms and signs. The ever-increasing pressure on the health care system requires finding an effective treatment that can benefit even advanced-stage patients such as those in the intensive care unit.

It was not until recently that the published literature about hydrogen sulfide shifted from revolving around its toxicity to its recognition as an endogenous gaseous signaling molecule and its biological roles. Hydrogen Sulfide (H2S) is a novel gaseous signaling molecule (gasotransmitter) that regulates a variety of physiological functions and provides protection against organ damage (anti-inflammatory, prolonged survival, cardioprotection, antioxidant, and more). H2S also displays beneficial roles in preventing lung disorders such as pneumonia, lung injury (acute/ chronic), and chronic obstructive pulmonary disease and limits viral replication. H2S has been shown to be effective in reversing lung inflammation and improving pulmonary function in various animal models. Based on preclinical data, cystathionine-γ-lyase (CSE)-derived H2S or exogenously applied H2S may block Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) entry into the host cells by interrupting Angiotensin-Converting Enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2), inhibiting viral replication by attenuating syncytium formation and virus assembly/release, and thus may protect SARS-CoV-2-induced lung damage by suppressing the immune response and the development of inflammation.

Lymphopenia is a key characteristic of COVID-19 patients. Serum H2S was positively correlated with the lymphocyte count and is considered a predictor of mortality. Additionally reduced H2S bioavailability has been suggested as an indicator of enhanced pro-inflammatory responses and endothelial dysfunction. Both these conditions often accompany severe COVID-19. Interleukin-6 (IL-6) has been proposed as the principle pro-inflammatory cytokine involved in the cytokine storm that leads to severe lung injury, respiratory failure, and death by COVID-19. A negative association between IL-6 and serum H2S has been shown to exist. The above-mentioned results led to further evaluation of admission H2S levels as a marker of survival in a recent study. Results showed that serum levels of H2S on day 1 lower than 150.44 micromolars (μM) had the best tradeoff for sensitivity and specificity for death. Thus, administration of a H2S-donor could be a potential remedy for COVID-19 by relieving the damage in lungs and other organs.

Sodium thiosulfate (STS) is a H2S-donor with known safety and efficacy profile in humans for other diseases, including calciphylaxis and cyanide poisoning. STS can be metabolized to H2S and acts as a precursor for H2S signaling. Moreover, in patients presenting with acute coronary syndrome, a phase 1 study was conducted, showing that STS was well tolerated, even with concomitant use of blood pressure lowering drugs. Additionally, the Groningen Intervention study for Preservation of cardiac function with Sodium thiosulfate in ST-elevation myocardial infarction (GIPS-IV trial) is the first trial in humans designed to test the hypothesis that STS provides protection against I/R injury in patients presenting with ST-segment elevation myocardial infarction

Conditions

COVID-19; Virus Diseases; Corona Virus Infection

Study Design

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

Study Groups

Standard Treatment

The standard treatment includes the application of mechanical ventilation and / or support with the administration of inotropes and / or extracorporeal oxygenation (ECMO) and the intravenous administration of fluids and dexamethasone. The administration of any other immunosuppressive therapy, including tocilizumab and / or antimicrobials at the discretion of the therapists, is permitted.

Group Type: NO_INTERVENTION

No interventions assigned to this group

One intravenous 12.5 gr STS - Treatment Group 1

Patients will receive standard treatment and one intravenous (iv)12.5 gr STS in 60 minutes continuous intravenous infusion. STS is dissolved in a final volume of 100ml N/S 0.9% w/v,

Group Type: EXPERIMENTAL

Sodium Thiosulfate 25% Solution for Injection

Intervention Type: DRUG

The drug will be administered via continuous infusion after being diluted to a concentration 12.5 gr/100ml

Three intravenous doses of 12.5 gr STS - Treatment Group 2

Patients will receive standard treatment and three intravenous doses of 12.5 g STS. STS is dissolved in a final volume of 100ml N/S 0.9% w/v. Each dose will be given in 60 minutes of continuous intravenous infusion with 48 hours intervals between each dose.

Group Type: EXPERIMENTAL

Sodium Thiosulfate 25% Solution for Injection

Intervention Type: DRUG

The drug will be administered via continuous infusion after being diluted to a concentration 12.5 gr/100ml

Interventions

Sodium Thiosulfate 25% Solution for Injection

The drug will be administered via continuous infusion after being diluted to a concentration 12.5 gr/100ml

Intervention Type: DRUG

Other Intervention Names

NATRIUMTHIOSULFAT 25%

Eligibility Criteria

Inclusion Criteria

1. Age equal to or older than 18 years

2. Both genders

3. For women of childbearing potential, they must use or be willing to use a dual contraceptive method during the study.

4. Written consent statement provided by the patient or his / her legal representative in case patients are unable to consent.

5. Confirmed COVID-19 disease

6. WHO-CPS 7 to 9

7. Hospitalization in Intensive Care Unit

8. Serum H2S levels less than 140 μM

Exclusion Criteria

1. Age less than 18 years

2. Denial of written consent

3. Decision not to resuscitate

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 110 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hellenic Institute for the Study of Sepsis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ioannis Alamanos, MD

Role: PRINCIPAL_INVESTIGATOR

General Hospital of Athens KAT

Locations

General Hospitan of Athens KAT 2nd Department of ICU

Athens, Kifisia, Greece

Site Status: RECRUITING

Countries

Greece

Central Contacts

Evangelos Giamarellos-Bourboulis, MD, PhD

Role: CONTACT

egiamarel@med.uoa.gr

+302107480662

Antigoni Kotsaki, MD, PhD

Role: CONTACT

scra@sepsis.gr

+306946637164

Facility Contacts

Ioannis Alamanos, MD

Role: primary

icualamanos@yahoo.gr

6932300372

Vasilios Kaldis, MD

Role: backup

vkaldis@yahoo.gr

6947520344

Other Identifiers

H4COVID

Identifier Type: -

Identifier Source: org_study_id