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Enriched Heparin Anti COVID-19 Trial (EnHanCed)

27 settembre 2021 aggiornato da: 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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Anticipato)

50

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Brasile
    • SP
      • Botucatu, SP, Brasile, 18607030
        • Non ancora reclutamento
        • School of Medicine at Botucatu- Paulista State University- UNESP, São Paulo, Brazil
        • Contatto:
        • Contatto:
        • Investigatore principale:
          • Matheus Bertanha, PhD
    • Sao Paulo
      • Botucatu, Sao Paulo, Brasile, 18618970
        • Reclutamento
        • Hospital das Clinicas de Boucatu
        • Contatto:
        • Contatto:
        • Investigatore principale:
          • Matheus Bertanha, Ph.D.
        • Sub-investigatore:
          • Pedro L Mellucci Filho, M.D.
        • Sub-investigatore:
          • Vinicius R Grillo, M.D.
        • Sub-investigatore:
          • Nathalia D Sertorio, M.D.

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore placebo: Placebo
Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses).
Droga: Placebo
Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)
Altri nomi:
  • Soluzione salina 0,9%
  • Physiological solution 0.9%
Comparatore attivo: 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).
Droga: 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)
Altri nomi:
  • Hepamax S BLAU

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in activated partial thromboplastin time (APTT) > 1.5
Lasso di tempo: 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).
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of participants needing supplemental oxygen therapy
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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 (%)
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

UPECLIN HC FM Botucatu Unesp

Investigatori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

1 giugno 2021

Completamento primario (Anticipato)

30 novembre 2021

Completamento dello studio (Anticipato)

31 dicembre 2021

Date di iscrizione allo studio

Primo inviato

3 febbraio 2021

Primo inviato che soddisfa i criteri di controllo qualità

5 febbraio 2021

Primo Inserito (Effettivo)

8 febbraio 2021

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

29 settembre 2021

Ultimo aggiornamento inviato che soddisfa i criteri QC

27 settembre 2021

Ultimo verificato

1 settembre 2021

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • UPECLIN-MB-2

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

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

Periodo di condivisione IPD

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

Criteri di accesso alla condivisione IPD

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.

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA
  • ICF
  • RSI

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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