Clinical Trial to Evaluate the Effectiveness and Safety of Tocilizumab for Treating Patients With COVID-19 Pneumonia

COVID-19 Clinical Trial

Official title:

A Multicentre, Open-label Clinical Trial to Evaluate the Effectiveness and Safety of Intravenous Tocilizumab for Treating Patients With COVID-19 Pneumonia: the BREATH-19 Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04445272
• Other study ID #: BREATH-19 (FSG011-20)
• Status: Completed
• Phase: Phase 2
• Start date: May 22, 2020
• Est. completion date: December 23, 2020

Study information

• Verified date: June 2020
• Source: Fundacion SEIMC-GESIDA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

At present, no treatment has been approved for COVID-19. However, in light of the increased interest on using the anti-cytokine therapy targeting IL-6 tocilizumab in COVID-19 infected patients due to its potential benefit, the Spanish Agency for Medicine and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) have initiated the controlled distribution of the drug. Tocilizumab is indeed proposed as a potential treatment for severe COVID-19 in Spain. Based on the positive results of tocilizumab in the treatment of COVID-19 patients and the experience of tocilizumab in inducing rapid reversal of CSS in other pathologies several clinical trials and observational studies are being conducted to assess the effectiveness and safety of tocilizumab in COVID-19 patients. Further studies with a large sample size are required to confirm the effectiveness of tocilizumab in patients with COVID-19 pneumonia. The need for the management of severe COVID-19 disease is imperative, and every effort should be made to collect relevant clinical outcomes. The aim of the present study is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia who are currently hospitalized or admitted to ICU by describing improvement of respiratory function and mortality rate. This large real-world cohort therefore provides a unique opportunity to study this potential medicine during the current emergency situation, and support the findings from other ongoing clinical trials and observational studies, such as the Roche-sponsored Phase III study that is planned to start early April.

Description:

Cytokine storm syndrome (CSS) is caused by the excessive release of cytokines during an exaggerated immune response. CSS can be triggered by infections or therapeutic interventions, being more severe depending on the degree and duration of immune activation. CSS is as a significant on-target side-effect of chimeric antigen receptor (CAR) T-cell therapies, which have been subject to assessment for the treatment of haematological malignancies. Tocilizumab (intravenous, IV) is indicated for the treatment of chimeric antigen receptor CAR T cell-induced severe or life-threatening CSS. Based on the experience with tocilizumab in the CSS, and that some patients infected with SARS-CoV-2 can develop CSS, leading to potentially fatal damage to lung tissue, the drug is being investigated in China and Italy, and clinical trials are being conducted/planned in these and several other countries. Real-word experience with tocilizumab IV have shown that in a substantial proportion of COVID-19 patients with severe pneumonia, fever returned to normal and respiratory function based on oxygen intake and lung opacities improved remarkably. Laboratory parameters such as C-reactive protein (CRP) that seem to be increased in patients infected decreased significantly with tocilizumab, and lymphocytes levels also returned to normal. All these findings have led the Spanish Agency for Medicine and Health Products (AEMPS) to initiate the controlled distribution of tocilizumab IV, in light of the increased interest on the anti-cytokine therapy targeting IL-6 in COVID-19 infected patients. Therefore, tocilizumab might be among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients. The aim of the present study is to evaluate the effectiveness and safety of IV tocilizumab in patients with COVID-19 severe pneumonia who are currently hospitalized or admitted to ICU. This large real-world cohort provides a unique opportunity to study a potential medicine during the current emergency situation, and support the findings from the Roche-sponsored Phase III study that is planned to start in early April.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 495
• Est. completion date: December 23, 2020
• Est. primary completion date: December 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Provide oral informed consent to participate in this study.
• At least 18 years of age.
• Diagnosed with COVID-19 pneumonia by RT-PCR.
• Have received the first dose of tocilizumab a maximum of two days before the inclusion or is candidate for tocilizumab treatment
• Hospitalized or admitted to ICU

Exclusion Criteria:

• The patient has any other medical condition or is receiving concomitant medication that could, in the opinion of the investigator, compromise the patient's safety or collected data
• Known severe allergic reactions to tocilizumab or other monoclonal antibodies
• Active acute and severe infections, including tuberculosis infection
• Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination

Related Conditions & MeSH terms

• COVID-19
• Pneumonia

Intervention

Drug:
• Tocilizumab
Treatment with Tocilizumab

Locations

Country	Name	City	State
Spain	Complejo Hospitalario Universitario de Albacete	Albacete
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid
Spain	Hospital Infanta Cristina	Badajoz
Spain	Hospital Clínic i Provincial Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid
Spain	Hospital Universitario de Galdakao	Galdakao	Bizkaia
Spain	Hospital Universitario Dr. Josep Trueta	Gerona
Spain	Hospital Universitario de Getafe	Getafe	Madrid
Spain	Hospital Universitario de Cabueñes	Gijón	Asturias
Spain	Hospital Universitario Clínico San Cecilio	Granada
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Jerez de la Frontera	Jerez De La Frontera	Cádiz
Spain	Hospital Universitari de Bellvitge	L'Hospitalet De Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Spain	Hospital Sant Joan de Déu de Manresa	Manresa	Barcelona
Spain	Hospital de Mataró	Mataró	Barcelona
Spain	Hospital Rey Juan Carlos	Móstoles	Madrid
Spain	Hospital Universitario Rey Juan Carlos	Móstoles	Madrid
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	Murcia
Spain	Complexo Hospitalario Universitario de Ourense	Orense
Spain	Hospital Universitari Son Espases	Palma De Mallorca	Islas Baleares
Spain	Complejo Hospitalario de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Salamanca	Salamanca
Spain	Hospital Universitario Infanta Sofía	San Sebastián De Los Reyes	Madrid
Spain	Hospital Universitario Marqués Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen de la Macarena	Sevilla
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Nuestra Señora del Prado	Talavera De La Reina	Toledo
Spain	Hospital Virgen de la Salud	Toledo
Spain	Hospital Público General del Tomelloso	Tomelloso	Ciudad Real
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Poliectenic La Fe	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (3)

Lead Sponsor	Collaborator
Fundacion SEIMC-GESIDA	Dynamic Science S.L., Roche Pharma AG

Country where clinical trial is conducted

Spain, 

References & Publications (1)

Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014 Mar-Apr;20(2):119-22. doi: 10.1097/PPO.0000000000000035. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To calulate the time of intubation	Calculate the mean time of intubation	through study completion, and average of 1 month
Primary	To calculate the time with oxygen therapy	Calculate the mean time with oxygen therapy	through study completion, and average of 1 month
Primary	To calculate the time with Non-invasive mechanical ventilation	Calculate the mean time with Non-invasive mechanical ventilation	through study completion, and average of 1 month
Primary	To evaluate mortality rate	Number of patients deaths of the total of patients included	through study completion, and average of 1 month
Secondary	To calculate respiratory function parameters	To calculate the mean ofPaO2/FiO2	through study completion, and average of 1 month
Secondary	To calculate respiratory function parameters	To calculate the mean of levels of oxygen saturation	through study completion, and average of 1 month
Secondary	To calculate respiratory function parameters	To calculate the mean of SaO2/FiO2	through study completion, and average of 1 month
Secondary	To evaluate radiological lung extension	Evaluate the lung extension of pneumonia	through study completion, and average of 1 month
Secondary	To evaluate radiological evolution	Evaluate the type of lung affection	through study completion, and average of 1 month
Secondary	To describe the duration of hospitalization and ICU use	Days of hospitalization in survivors and/or days at ICU throughout the study	through study completion, and average of 1 month
Secondary	To evaluate the requirement of additional organ support	Percentage of patients with extracorporeal membrane oxygenation	through study completion, and average of 1 month
Secondary	To evaluate the requirement of additional organ support	Percentage of patients with molecular adsorbent recirculating system	through study completion, and average of 1 month
Secondary	To evaluate the requirement of additional organ support	Percentage of patients with dialysis	through study completion, and average of 1 month
Secondary	To evaluate the requirement of additional organ support	Percentage of patients with other support therapy	through study completion, and average of 1 month
Secondary	To evaluate the effect of IV tocilizumab on the serum levels of inflammatory markers	Analyze the levels of IL-6	through study completion, and average of 1 month
Secondary	To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab	Incidence of adverse events	through study completion, and average of 1 month
Secondary	To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab	Incidence of adverse events by dose of Tocilizumab	through study completion, and average of 1 month
Secondary	To assess time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity	To evaluate the time to RT-PCR virus negativity	through study completion, and average of 1 month
Secondary	To evaluate the effect of IV tocilizumab on the serum levels of inflammatory	Analyze the levels of CRP	through study completion, and average of 1 month
Secondary	To evaluate the effect of IV tocilizumab on the serum levels of inflammatory	Analyze the levels of procalcitonin (PCT)	through study completion, and average of 1 month
Secondary	To evaluate the effect of IV tocilizumab on the serum levels of inflammatory	Analyze the levels of ID-dimer	through study completion, and average of 1 month
Secondary	To evaluate the effect of IV tocilizumab on the serum levels of inflammatory	Analyze the levels of ferritin	through study completion, and average of 1 month
Secondary	To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab	Indicende of serious adverse events	through study completion, and average of 1 month
Secondary	To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab	Indicende of serious adverse events based on dose of Tocilizumab	through study completion, and average of 1 month
Secondary	To calculate the number of adverse events of special interest in patients with COVID-19 pneumonia treated with Tocilizumab	Indicende of adverse events of special interest based on dose of Tocilizumab	through study completion, and average of 1 month
Secondary	To evaluate mortality rate	Number of patients deaths of the total of patients included based on dose of Tocilizumab	through study completion, and average of 1 month
Secondary	To evaluate respiratory function	Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on dose of Tocilizumab	through study completion, and average of 1 month
Secondary	To evaluate mortality rate	Number of patients deaths of the total of patients included based on severity of disease at the start of the study treatment	through study completion, and average of 1 month
Secondary	To evaluate mortality rate	Number of patients deaths of the total of patients included based on presence of cytokine storm syndrome at the start of treatment	through study completion, and average of 1 month
Secondary	To evaluate respiratory function	Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on severity of disease at the start of the study treatment	through study completion, and average of 1 month
Secondary	To evaluate respiratory function	Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on presence of cytokine storm syndrome at the start of treatment	through study completion, and average of 1 month