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Enriched Heparin Anti COVID-19 Trial (EnHanCed)

27. september 2021 oppdatert av: Matheus Bertanha, PhD, UPECLIN HC FM Botucatu Unesp

Nebulized Enriched Heparin to Treat no Critical Patients With Sars-Cov-2 - Triple Blind Clinical Trial

Coronavirus 19 (COVID-19) is a viral respiratory disease that was identified in December 2019 after the first cases in China, spreading rapidly until reaching pandemic status, causing the collapse of numerous health systems and strong economic and social impact. By the end of April 2020, 3.08 million cases, and more than 214 thousand deaths were already recorded. The treatment so far has not been established and there are several clinical trials testing known drugs that have antiviral activity in vitro, due to the urgency that the global situation imposes. Medicines with specific actions can take years to be discovered, while a vaccine also takes a long time. Recently, it has been shown that the worsening of Coronavirus infection may be related to the formation of micro clots in blood vessels and anticoagulants have been used as adjuvants in the treatment. This study is justified by conducting a pilot study that showed an in vitro antiviral action (anti-COVID-19) of high molecular weight heparin. Methods: A phase I / II clinical trial will be conducted. 40 participants will be included in two arms. Participants allocated to Group 1 (control) will receive inhalation with 0.9% saline applied 4/4 hours, for 7 days. Participants allocated to Group 2 (intervention) will receive high molecular weight inhaled heparin (250ug / mL 0.9% SF), at a 4/4 hour dose, for 7 days. The outcomes of interest will be safety (absence of moderate or serious adverse events) and effectiveness (measured in a score of 7 points, with 1 absence of limitations and 7, death). Expected results: The development of a new therapeutic option for COVID-19 is expected, with the possibility of use in other serious coronavirus diseases, to be subsequently tested in phase III studies.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

In view of the enormous health, financial and social crisis resulting of the pandemic caused by SARS-Cov-2, it is justified to urgently conduct tests with possible antiviral drugs. The high molecular weight heparin (HMWH) (heparin enriched by ultrafiltration process) proposed by this study, has a potential inhibition activity over viral replication, demonstrated by preliminary in vitro tests, carried out in a model established in partnership with the Laboratory of Clinical and Molecular Virology (LVCM) of the Institute of Biomedical Sciences of the University of São Paulo (ICB-USP).

Along with the findings in the literature, such as the study carried out by Phelps, M.K. et al (2020), among others, the use of inhaled heparin presents adequate levels of safety to be used in a clinical trial. Taking into account that the dose of high molecular weight heparin (enriched by this study team) with antiviral activity in vitro is much lower than the doses currently presented in published clinical trials using inhaled UFH, we have the safety premise to carry out this study. The intentions of this study differ from what has been presented in the world literature so far, as it does not aim to induce anticoagulation, nor to effectively inhibit the formation of pulmonary fibrin, but rather, to act as an inhibitor of viral replication.

Also, as characteristics of the product to be tested, this heparin (HMWH) is presented in a buffered solution free of low-sulfated low-weight molecules, which is obtained in a sterile environment through ultrafiltration of the unfractionated solution of porcine origin available in Brazil (Hemofol - Cristália) using Centriprep-10kDa® centrifuge filter (Millipore ™) used as recommended by the manufacturer.

The high molecular weight heparin (HMWH) - enriched heparin - had two process patents filed, one under the description "HIGH MOLECULAR WEIGHT DEFINITION HEPARINE DEVELOPMENT PROCESS", BR 102014027804-4 A2 - granted by the Instituto Nacional de Propriedade Industrial (INPI) and another with the description "COMPOSITION OF HIGH MOLECULAR WEIGHT NON-FRACTIONAL HEPARINE FOR ANTIVIRAL ACTION ", BR 102020 011964-8 - deposited at INPI.

Studietype

Intervensjonell

Registrering (Forventet)

50

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Brasil
    • SP
      • Botucatu, SP, Brasil, 18607030
        • Har ikke rekruttert ennå
        • School of Medicine at Botucatu- Paulista State University- UNESP, São Paulo, Brazil
        • Ta kontakt med:
        • Ta kontakt med:
        • Hovedetterforsker:
          • Matheus Bertanha, PhD
    • Sao Paulo
      • Botucatu, Sao Paulo, Brasil, 18618970
        • Rekruttering
        • Hospital das Clinicas de Boucatu
        • Ta kontakt med:
        • Ta kontakt med:
        • Hovedetterforsker:
          • Matheus Bertanha, Ph.D.
        • Underetterforsker:
          • Pedro L Mellucci Filho, M.D.
        • Underetterforsker:
          • Vinicius R Grillo, M.D.
        • Underetterforsker:
          • Nathalia D Sertorio, M.D.

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Signature and agreement to the Free Consent Form;
  • Both sexes, of any ethnic origin, aged between 18 and 90 years;
  • COVID-19 infected patients diagnosed by RT-PCR (reverse-transcriptase polymerase chain reaction) or with a strong suspicion of COVID-19 by clinical evaluation through compatible clinical and radiological findings;
  • Time of disease evolution less than 10 days;
  • Radiological diagnosis of grade 2A pneumonia, with gas exchange ratio > 200 on blood gas analysis (paO2 / pFiO2), characterizing mild hypoxemia;
  • Indication of hospital treatment regime, provided that the period of hospitalization before inclusion is not more than 24 hours;
  • Need for supplemental oxygen therapy (O2) less than 5L / min.

Exclusion Criteria:

  • No agreement to the terms of this study;
  • Moderate or severe respiratory failure requiring admission to the ICU and the need for invasive mechanical ventilation or non-invasive ventilation (NIV) with positive pressure;
  • Pregnancy or puerperium;
  • Patients with hematological diseases, coagulation disorders, use of anticoagulants, previous heparin-induced allergy or thrombocytopenia, thrombocytopenia with a count of fewer than 50,000 platelets / mm3;
  • COVID-19 not confirmed by RT-PCR within 72 hours of inclusion in the study.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Placebo komparator: Placebo
Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses).
Legemiddel: Placebo
Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)
Andre navn:
  • Saltoppløsning 0,9 %
  • Physiological solution 0.9%
Aktiv komparator: Heparin sodium
Participants will receive inhalation with 5mL 0.9% saline solution + 2,5mg of high molecular weight heparin - enriched heparin, 4/4h, during the day period (5 doses).
Legemiddel: Heparin sodium
Nebulized inhalation of 5 mL of a solution containing high molecular weight heparin - enriched heparin - 2.5mg/mL and 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)
Andre navn:
  • Hepamax S BLAU

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change in activated partial thromboplastin time (APTT) > 1.5
Tidsramme: Immediately or up to 8 days after starting treatment
Safety-related to the use of high molecular weight heparin inhaled in patients with SARS-COV-2 through the assessment of hemorrhagic events of any nature, alteration of the coagulogram that indicates an increase in APTT> 1.5, heparin-induced thrombocytopenia.
Immediately or up to 8 days after starting treatment
Viral load in nasal swab reverse transcription polymerase chain reaction (RT-PCR).
Tidsramme: Immediately or up to 8 days after starting treatment
Effectiveness related to the proposed treatment, based on the analysis of the viral load of SARS-COV-2 virus in the participants through a sequential assessment of the viral load in nasal swab RT-PCR.
Immediately or up to 8 days after starting treatment

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of participants needing supplemental oxygen therapy
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of respiratory parameters measured by the need for supplemental oxygen therapy at greater doses than 5L/min;
Immediately or up to 8 days after starting treatment
Number of participants needing mechanical pulmonary ventilation
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of respiratory parameters measured by the need of definitive airway assisted pulmonary ventilation;
Immediately or up to 8 days after starting treatment
Number of hospitalization days
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of clinical parameters characterized by a prolonged hospital stay;
Immediately or up to 8 days after starting treatment
Number of participants that develop renal failure
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of clinical parameters characterized by renal failure through measurement of urea and creatinine;
Immediately or up to 8 days after starting treatment
Number of participants that develop major cardiovascular events
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of clinical parameters characterized by major cardiovascular events (pulmonary embolism, acute myocardial infarction)
Immediately or up to 8 days after starting treatment
Number of participants transferred to the intensive care unit (ICU)
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of clinical parameters characterized by need for Intensive Care Unit (ICU) treatment;
Immediately or up to 8 days after starting treatment
Number of participants presenting secondary pulmonary bacterial infections
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of clinical parameters characterized by presentation of secondary pulmonary bacterial infections (pneumonia);
Immediately or up to 8 days after starting treatment
Number of participants that develop deep vein thrombosis (DVT)
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of clinical parameters characterized by deep vein thrombosis (DVT);
Immediately or up to 8 days after starting treatment
Number of participants that develop pancreatitis
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of clinical parameters characterized by pancreatitis through measurement of amylase (> 200 U/L);
Immediately or up to 8 days after starting treatment
Number of participants that need corticosteroid therapy
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of clinical parameters characterized by need for hydrocortisone, dexamethasone or other corticosteroids due to inflammatory pulmonary disease;
Immediately or up to 8 days after starting treatment
Number of deaths among participants
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of clinical parameters characterized by death;
Immediately or up to 8 days after starting treatment
Number of participants with increased white blood cell count
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of laboratory parameters measured by increased white blood cell count (>10.000 cells/mm³);
Immediately or up to 8 days after starting treatment
Number of participants with increased C reactive protein test
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of laboratory parameters measured by increase in C reactive protein test (>3.00mg/L);
Immediately or up to 8 days after starting treatment
Number of participants with deterioration of arterial blood gas paO2/pFiO2 ratio
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of laboratory parameters measured by alterations in arterial blood gas measured by paO2/pFiO2 < 200;
Immediately or up to 8 days after starting treatment
Number of participants with altered sodium
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of laboratory parameters measured by alterations in sodium (< 135mEq/L or > 145mEq/L)
Immediately or up to 8 days after starting treatment
Number of participants with altered potassium
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of laboratory parameters measured by alterations in potassium (< 3,5mEq/L or > 5,5mEq/L);
Immediately or up to 8 days after starting treatment
Number of participants with increased pulmonary area compromised (%)
Tidsramme: Immediately or up to 8 days after starting treatment
Worsening of tomographic parameters measured by the pulmonary area compromised by the infection and/or inflammation.
Immediately or up to 8 days after starting treatment

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

UPECLIN HC FM Botucatu Unesp

Etterforskere

  • Hovedetterforsker: Matheus Bertanha, PhD, São Paulo State University (Unesp)

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

1. juni 2021

Primær fullføring (Forventet)

30. november 2021

Studiet fullført (Forventet)

31. desember 2021

Datoer for studieregistrering

Først innsendt

3. februar 2021

Først innsendt som oppfylte QC-kriteriene

5. februar 2021

Først lagt ut (Faktiske)

8. februar 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

29. september 2021

Siste oppdatering sendt inn som oppfylte QC-kriteriene

27. september 2021

Sist bekreftet

1. september 2021

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • UPECLIN-MB-2

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

There is a plan to make IPD and related data dictionaries available

IPD-delingstidsramme

The summary data will be published or made available 6 months after publication.

Tilgangskriterier for IPD-deling

Epidemiological data, clinical data, and patient evolution will be shared during the study only for researchers who request access to the data. Access requests will be analyzed by the main researcher, and they will only be released for scientific purposes.

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • SEVJE
  • ICF
  • CSR

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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