Compassionate use of tocilizumab in hantavirus pulmonary syndrome: a pre- and post-study
| ISRCTN | ISRCTN72088243 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN72088243 |
| Secondary identifying numbers | TOCIHPS2024 |
- Submission date
- 14/05/2024
- Registration date
- 26/06/2024
- Last edited
- 26/06/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Background and study aims
Hantavirus Pulmonary Syndrome (HPS) is a severe and sometimes fatal respiratory disease caused by infection with hantavirus. Current treatments are primarily supportive, and there is a need for more effective therapies. This study investigates whether tocilizumab, a drug used to reduce inflammation in other diseases, can improve survival rates in patients with HPS.
Who can participate?
Adults aged 18 years or older who have been diagnosed with Hantavirus Pulmonary Syndrome and are admitted to the hospital
What does the study involve?
Participants will receive a single dose of tocilizumab administered intravenously (through a vein) within the first 24 hours of their hospital admission. Their health will be monitored closely throughout their hospital stay to observe the effectiveness and safety of the treatment.
What are the possible benefits and risks of participating?
The potential benefit of participating in this study is the possible reduced risk of death from HPS. The risks include side effects related to tocilizumab, such as possible allergic reactions and increased susceptibility to infections. All participants will receive standard medical care for HPS in addition to the study treatment.
Where is the study run from?
Hospital Zonal Bariloche "Ramón Carrillo" (Argentina)
When is the study starting and how long is it expected to run for?
February 2024 to August 2029
Who is funding the study?
1. Hospital Zonal Bariloche "Ramón Carrillo" (Argentina)
2. Rio Negro National University (Argentina)
Who is the main contact?
Dr Fernando Tortosa, fgtortosa@unrn.edu.ar
Contact information
Dr Fernando Tortosa
Public, Scientific, Principal Investigator
Public, Scientific, Principal Investigator
Moreno 601
San Carlos de Bariloche
R8402HVG
Argentina
 ORCID ID |
0000-0002-0303-6055 |
|---|---|
| Phone | +54 (0)294154357104 |
| fgtortosa@unrn.edu.ar |
Study information
| Study design | Pre-post intervention study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital, Medical and other records |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A pre- and post-intervention study to assess the efficacy of tocilizumab in reducing mortality in hantavirus pulmonary syndrome |
| Study acronym | HPS-TOCI-Reduction |
| Study hypothesis | The hypothesis of this study is that the administration of tocilizumab will reduce the mortality rate among patients with Hantavirus Pulmonary Syndrome (HPS) by 25% compared to the historical mortality rate without this treatment. |
| Ethics approval(s) |
Approved 07/05/2024, Comisión ética de Evaluación de Protocolos de Estudios de Investigación en Salud Humana de la Provincia de Río Negro (CEEPISH) (Viedma, Rio Negro, Viedma, 8400, Argentina; +54 (0)92944578364; investigacionrionegro@gmail.com), ref: 185470-S-2024 |
| Condition | Hantavirus pulmonary syndrome |
| Intervention | In this pre-post intervention study, all participants diagnosed with Hantavirus Pulmonary Syndrome (HPS) receive tocilizumab in addition to standard care. The study assesses the mortality rate before and after the intervention, comparing historical mortality data from patients with similar demographic and clinical profiles who did not receive tocilizumab. Tocilizumab is administered as a single intravenous dose of 8 mg/kg, up to a maximum of 800 mg, within the first 24 hours of hospital admission. The primary outcome measure is the mortality rate at 28 days post-intervention. The study is conducted in a hospital setting, ensuring that all participants are monitored for safety and efficacy outcomes. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Tocilizumab |
| Primary outcome measure | Mortality measured using medical records at 28 days post-intervention |
| Secondary outcome measures | 1. Incidence of mechanical ventilation measured using medical records at the time of hospital admission, daily during hospital stay, and at discharge 2. Duration of mechanical ventilation, measured using medical records from the initiation to the cessation of mechanical ventilation during the hospital stay 3. Incidence of inotropic support measured using medical records at the time of hospital admission, daily during hospital stay, and at discharge |
| Overall study start date | 15/02/2024 |
| Overall study end date | 31/08/2029 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | All |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | Both |
| Target number of participants | 30 |
| Participant inclusion criteria | 1. Diagnosis confirmation: participants must be clinically diagnosed with Hantavirus Pulmonary Syndrome. Diagnosis should be confirmed through one or more of the following: 1.1. Detection of hantavirus-specific IgM antibodies in serum. 1.2. A four-fold rise in hantavirus-specific IgG antibody titers in paired serum samples. 1.3. Positive RT-PCR test for hantavirus RNA in blood or tissue samples. 2. Age: participants must be aged 18 years or older. This age criterion ensures that all participants can legally consent to the study and are within the adult age range most commonly affected by HPS. 3. Severity of condition: participants must be exhibiting symptoms severe enough to require hospitalization, ensuring the study targets those most likely to benefit from tocilizumab treatment. 4. Ability to provide informed consent: participants must be capable of giving informed consent or have a legal guardian who can consent on their behalf if they are incapacitated. 5. Treatment window: participants must be eligible to receive the study intervention (tocilizumab) within 24 hours of hospital admission to ensure the treatment is administered in a timely manner, which is critical for its potential efficacy. 6. Health status: participants must have no known allergies to tocilizumab or its excipients. 7. No severe co-morbid conditions that could interfere with the study outcomes or significantly increase the risk of adverse effects from tocilizumab, such as severe chronic liver disease, known active tuberculosis, or other severe active infections. 8. No prior treatment: participants must not have received tocilizumab or other investigational treatments for HPS before enrollment in this study to ensure that any observed effects can be attributed to the study drug. |
| Participant exclusion criteria | 1. Previous treatment with tocilizumab or related therapies: participants who have previously received tocilizumab or other monoclonal antibodies targeting IL-6 or IL-6 receptors for any condition. 2. Severe allergic reactions: individuals with a history of severe allergic reactions to tocilizumab or any of its excipients. 3. Active or latent infections: participants with active, severe infections at the time of screening, such as tuberculosis, HIV, or hepatitis. 4. Individuals with a known history of chronic or recurrent infections. 5. Pregnancy or lactation: pregnant or breastfeeding women due to the unknown effects of tocilizumab on fetuses or infants. 6. Severe comorbid conditions: individuals with uncontrolled cardiovascular, liver, renal, or metabolic diseases that could complicate treatment outcomes. 7. Patients with a known history of gastrointestinal perforation within the last 6 months. 8. Recent vaccinations: participants who have received live vaccines within 30 days prior to the intended start of treatment. 9. Participation in other clinical trials: individuals currently participating in another clinical trial or who have participated in a clinical trial involving an investigational product within the last 30 days. 10. Substance abuse: current or recent (within the last year) history of significant alcohol or drug abuse that could interfere with adherence to study protocols. 11. Immunosuppression: patients with conditions or on treatments that significantly suppress immune function, such as chemotherapy or high-dose corticosteroids. 12. Psychiatric illness: individuals with psychiatric illnesses or conditions that could interfere with their ability to understand or comply with the requirements of the study. |
| Recruitment start date | 01/06/2024 |
| Recruitment end date | 31/12/2028 |
Locations
Countries of recruitment
- Argentina
- Chile
Study participating centre
Hospital Zonal Bariloche "Ramón Carrillo"
Moreno 601
San Carlos de Bariloche
R8402HVG
Argentina
San Carlos de Bariloche
R8402HVG
Argentina
Sponsor information
Ministerio de Salud de Rio Negro
Hospital/treatment centre
Hospital/treatment centre
San Carlos de Bariloche
San Carlos de Bariloche
R8402HVG
Argentina
| Phone | +54 (0)294154357104 |
|---|---|
| investigacion.andina@unrn.edu.ar | |
| Website | https://www.hospitalbariloche.com.ar/ |
Funders
Funder type
Hospital/treatment centre
"Ramon Carrillo" Bariloche Hospital
No information available
Rio Negro National University
No information available
Results and Publications
| Intention to publish date | 30/05/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository, Available on request, Published as a supplement to the results publication |
| Publication and dissemination plan | 1. Academic Journals: Primary Publication: The main findings will be submitted to a peer-reviewed journal that specializes in infectious diseases, public health, or pharmacology. Priority will be given to open-access journals to ensure wide accessibility. Secondary Publications: Subsequent analyses, including subgroup analyses and long-term outcomes, will be targeted at specialty journals relevant to virology, emergency medicine, and critical care. 2. Scientific Conferences: Conference Presentations: Results from the study will be presented at major international and regional conferences in the fields of infectious diseases, public health, and emergency medicine. These include presentations at the annual meetings of the Infectious Diseases Society of America (IDSA) and the World Health Organization’s annual public health forums. Posters and Workshops: In addition to oral presentations, findings will be shared through poster sessions and interactive workshops to engage with other researchers and clinicians actively. 3. Healthcare Professional Outreach: Continuing Medical Education (CME): Webinars and CME courses will be organized to educate healthcare providers on the implications of the study findings, focusing on how tocilizumab can be integrated into current treatment protocols for HPS. Professional Newsletters and Bulletins: Regular updates and summaries of the study progress and findings will be distributed through newsletters circulated to medical professionals and public health officials. 4. Public Engagement: Press Releases: Key milestones and results will be communicated through press releases distributed to major news outlets to reach a broader audience. Public Health Campaigns: Collaborate with public health agencies to integrate findings into public health campaigns, emphasizing the prevention and management of HPS. 5. Online and Social Media: Website Updates: Create a dedicated section on the study’s website for publishing regular updates, participant stories, and detailed explanations of the research findings. Social Media Channels: Utilize platforms such as Twitter, LinkedIn, and Facebook to share updates, infographics, and short videos that highlight study milestones and results. 6. Patient and Community Outreach: Community Forums: Hold community forums and Q&A sessions in areas most affected by HPS to discuss the study findings, treatment options, and preventive measures. Patient Advocacy Groups: Engage with patient advocacy groups to disseminate information through their networks and gather feedback on patient-centered care improvements. 7. Academic Collaborations and Policy Impact: Policy Briefs: Develop policy briefs aimed at health policymakers to inform them of the study results and suggest changes to national and international guidelines for managing HPS. Academic Partnerships: Collaborate with academic institutions to ensure ongoing research into HPS treatment options and to foster a new generation of researchers in this field. |
| IPD sharing plan | The datasets generated and/or analyzed during the current study will be stored in a publicly available repository to ensure transparency and accessibility. The datasets will also be available upon request from qualified researchers to facilitate further research and validation of the findings. Contact name and email address: Dr Fernando Tortosa fgtortosa@unrn.edu.ar Datasets generated during the study will be published as a supplement to the results publication to provide comprehensive access to the research data. Future data-sharing plans are not finalized at this stage. The details will be established based on the study’s progression and outcomes and will be made available at a later date. Type of Data: The study will collect clinical data, treatment outcomes, and adverse event reports related to the use of tocilizumab in treating Hantavirus Pulmonary Syndrome. Timing of Data Availability: Data will be available after the completion of the study and publication of the main results, expected to be around the end of 2028. Access Criteria: Data will be accessible to researchers who provide a methodologically sound proposal that is approved by an independent review committee associated with the data repository. Data Sharing Mechanism: Interested researchers will be required to sign a data access agreement to ensure the confidentiality and proper use of the data. Consent for Data Sharing: Participants will be informed about the data sharing plan, and their consent will include permission to share de-identified data with external researchers under controlled conditions. Ethical Considerations and Legal Compliance: All data sharing will comply with ethical standards, legal requirements, and guidelines set forth by regulatory bodies. Data will be anonymized or de-identified to protect participant privacy. |
Editorial Notes
15/05/2024: Study's existence confirmed by the Comisión ética de Evaluación de Protocolos de Estudios de Investigación en Salud Humana de la Provincia de Río Negro (CEEPISH).
