Survival TRial Using CytoKines in COVID-19 (STRUCK Trial)

NCT04724629 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 402422/2020-1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

Currently, there are few approved treatments for COVID-19, antiretroviral (remdesivir) and corticoids. With about 15% of COVID-19 patients suffering from severe disease health system will be overwhelmed. Treatments approaches to inhibit viral replication (antiretroviral and extended spectrum antiviral drugs), such as Remdesivir and Hydroxychloroquine are being used. In severe cases, by CT scans investigators are able to observe that these patients seem to be dying with fibrosis and lung vasculitis. It is hypothesised that targeting vasculitis and lung inflammation secondary to the viral infection may help patients' survival (reducing mortality) and/or decrease time in mechanical ventilators. It is proposed a 4-arm trial, converted to 2 after interim analysis (60 patients for the initial phase, sample size recalculation after initial analysis and 2 arms beyond). In initial phase, IL-6 indirect inhibitor (colchicine), in first arm; IL-17 inhibitor, an innovative target never tested (at this moment) in COVID-19 severe patients, in second study arm. Both approaches (indirect IL-6 and Il-17) are related to modulation of inflammatory immune response. Finally, in third arm, IL-2 low dose. This cytokine was identified as Treg upregulation. Treg levels decrease in hepatitis C virus (HCV) associated vasculitis and increase in vasculitis resolution. In fourth arm, control group, standard of care. Initially, for the first 60 included patients, the study will comprise 4 arms (15 patients per arm, randomization ratio 1:1:1:1). An interim effectiveness and safety analysis at this point will guide the selection of one single treatment strategy (adaptative study) to be carried on after that, comparatively with the control group. The multi-site trial planned enrollment duration of 4-6 months and for each participant will be approximately 4 weeks. This trial will bring complementary data to the global effort in COVID-19 cases resolution.

Conditions

Covid19

Keywords

Colchicine; Ixekizumab; Cytokine storm; Lung vasculitis; Recombinant Human Interleukin-2

Outcome Measures

Primary Outcomes (1)

• Ordinal scale of seven World Health Organization (WHO) categories of IL-17 inhibitor versus low dose IL-2 versus indirect IL-6 inhibitor (colchicine) versus standard treatment in the treatment of severe COVID-19

  proportion of patients with clinical improvement, defined by an increase of two points in the ordinal scale of seven WHO categories

  On the 21st day of study, since inclusion.

Secondary Outcomes (7)

• Time until independence from oxygen therapy in days

  During the follow-up period (30 days (+/- 2))

• Ventilator free days (in days)

  During the follow-up period (30 days (+/- 2))

• Assessment of worsening pulmonary involvement, defined as the presence of one of these criteria (absence or presence)

  At some point in Day 7, Day 14 and Day 28

• In patients who needed mechanical ventilation, time to indicate mechanical ventilation

  Day 0 up to 45 days

• Duration of hospitalization, in survivors

  On day 28

Other Outcomes (5)

• Correlation among the inflammatory proteins D-dimer, C- reactive protein (CRP), Lactate Dehydrogenase (LDH) Test, and ferritin with:

  During the follow-up period (30 days (+/- 2))

• Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, C-Reactive protein (CRP), ferritin (if applicable), D-dimer (if applicable)

  at Day 0, Day 2, Day 4, Day 7, Day 14, Day 21 and Day 28 after randomization;

• Change in Score for Sepsis (SOFA score)

  On days 7 and 14 of randomization

Study Arms (4)

IL-17 inhibitor (Ixekizumab)

EXPERIMENTAL

Patients will receive study medication Ixekizumab 80 mg per week, (SC) once a week for 4 weeks or until discharge.

Biological: Ixekizumab

IL-2 (Aldesleukin)

EXPERIMENTAL

1.5 million IU per day (SC) for 7 days or until discharge. Patients will receive study medication Aldesleukin 1.5 million IU per day (SC), for 7 days or until discharge.

Biological: Aldesleukin

Indirect IL-6 inhibitor (Colchicine)

EXPERIMENTAL

Patients will receive study medication colchicine 0.5 mg every 8 hours for 3 days (PO), followed by 4 weeks (+/-7 days) 0.5 mg twice daily. If a dose is missed, it should not be replaced.

Drug: Colchicine

Standard of care

ACTIVE COMPARATOR

Standard treatment, supplementation of O2 ventilation + standard treatment of the institution, which may include Dexamethasone according to the institutional protocol.

Drug: Standard of care (SOC)

Interventions

Ixekizumab BIOLOGICAL

80 mg of IL-17 inhibitor

Also known as: Taltz

IL-17 inhibitor (Ixekizumab)

Aldesleukin BIOLOGICAL

1.5 million IU (low-dose) of IL-2

Also known as: Proleukin

IL-2 (Aldesleukin)

Colchicine DRUG

0.5 mg of indirect IL-6 inhibitor

Indirect IL-6 inhibitor (Colchicine)

Standard of care (SOC) DRUG

Active comparator (Corticoids and antiretrovirals)

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Positive result in the quantitative real-time PCR (qPCR) test for SARS-CoV-2 in the respiratory tract;
• Pneumonia confirmed by chest imaging and
• Respiratory rate ≥ 24 IRPM (for adults) or
• O2 saturation \<93% or
• No improvement in O2 saturation, despite oxygen supply or
• Arterial hypotension; or
• Changes in capillary filling time; or
• Changes in the level of consciousness; or
• Oliguria;
• IMPORTANT: The presence of increased respiratory rate or desaturation (items "a" and "b") are criteria for hospital admission. Items "c" to "g" are considered criteria for ICU admission
• Following the recommendations of The São Paulo State Health Secretariat, resolution SS-28 of 03-Mar-2020, prepared by the Hospital das Clínicas of Medical School-USP.

You may not qualify if:

• Age \<18 years;
• Refuse to sign the Informed Consent Form;
• Patient's decision that their involvement is not in their interest;
• Severe known liver disease (eg cirrhosis, with aminotransferase levels\> 5 times the reference value limit);
• Pregnancy or breastfeeding period;
• Severe bacterial infection;
• Severe diarrhea;
• Diverticulitis or intestinal perforation;
• Infection known as HIV;
• Presence of one of the following uncontrolled or unstable cardiovascular diseases: stroke, ECG confirmed acute ischemia or myocardial infarction and / or clinically significant dysrhythmia; • Known history of gastrointestinal bleeding, uncontrolled peptic ulcer or uncontrolled duodenal ulcer;
• Known history of hemophilia or other bleeding disorders;
• History of organ transplantation, congenital immunodeficiency;

Sponsors & Collaborators

• University of Sao Paulo: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator
• Science Valley Research Institute: collaborator

Study Sites (2)

Faculdade de Medicina de Ribeirão Preto - USP

Ribeirão Preto, São Paulo, Brazil

Location

Hospital e Maternidade Christovão da Gama

Santo André, São Paulo, 09030-010, Brazil

Location

MeSH Terms

Conditions

COVID-19; Cytokine Release Syndrome

Interventions

ixekizumab; aldesleukin; Colchicine; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Fernando Rodrigues, MD, PhD

  Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, USP, SP, Brazil

  PRINCIPAL INVESTIGATOR

• Eduardo Ramacciotti, MD, PhD

  Hospital e Maternidade Dr. Christóvão da Gama, Grupo Leforte, Santo André, SP, Brazil

  STUDY CHAIR

• Leandro B Agati, PhD

  Hospital Leforte Liberdade, SP, Brazil

  STUDY DIRECTOR

• Esper Kallas, MD, PhD

  Hospital das Clinicas de Sao Paulo (USP)

  STUDY CHAIR

• Renato D Lopes, MD, PhD

  Duke University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated Professor - Dept of Social Medicine

Model Details: This is a multicenter, adaptive, open-label, randomized study design (1: 1: 1: 1 ratio), with an active comparator, superiority study, in severe to critical COVID19 subjects.

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: January 26, 2021
• Study Start: January 5, 2021
• Primary Completion: March 31, 2021
• Study Completion: July 30, 2021
• Last Updated: July 28, 2022

Record last verified: 2022-07

Locations

BR (2)