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Enriched Heparin Anti COVID-19 Trial (EnHanCed)

2021年9月27日 更新者：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.

調査の概要

状態

募集

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (予想される)

50

段階

  • フェーズ2
  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

  • ブラジル
    • SP
      • Botucatu、SP、ブラジル、18607030
        • まだ募集していません
        • School of Medicine at Botucatu- Paulista State University- UNESP, São Paulo, Brazil
        • コンタクト：
        • コンタクト：
        • 主任研究者：
          • Matheus Bertanha, PhD
    • Sao Paulo
      • Botucatu、Sao Paulo、ブラジル、18618970
        • 募集
        • Hospital das Clinicas de Boucatu
        • コンタクト：
        • コンタクト：
        • 主任研究者：
          • Matheus Bertanha, Ph.D.
        • 副調査官：
          • Pedro L Mellucci Filho, M.D.
        • 副調査官：
          • Vinicius R Grillo, M.D.
        • 副調査官：
          • Nathalia D Sertorio, M.D.

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
プラセボコンパレーター：Placebo
Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses).
薬：Placebo
Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)
他の名前：
  • 生理食塩水 0.9%
  • Physiological solution 0.9%
アクティブコンパレータ：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).
薬：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)
他の名前：
  • Hepamax S BLAU

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Change in activated partial thromboplastin time (APTT) > 1.5
時間枠：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).
時間枠：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

二次結果の測定

結果測定
メジャーの説明
時間枠
Number of participants needing supplemental oxygen therapy
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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 (%)
時間枠：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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

UPECLIN HC FM Botucatu Unesp

捜査官

  • 主任研究者：Matheus Bertanha, PhD、São Paulo State University (Unesp)

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2021年6月1日

一次修了 (予想される)

2021年11月30日

研究の完了 (予想される)

2021年12月31日

試験登録日

最初に提出

2021年2月3日

QC基準を満たした最初の提出物

2021年2月5日

最初の投稿 (実際)

2021年2月8日

学習記録の更新

投稿された最後の更新 (実際)

2021年9月29日

QC基準を満たした最後の更新が送信されました

2021年9月27日

最終確認日

2021年9月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • UPECLIN-MB-2

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

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

IPD 共有時間枠

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

IPD 共有アクセス基準

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 共有サポート情報タイプ

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

COVID19の臨床試験

Placeboの臨床試験

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スポンサーと協力者

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薬物療法

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条件

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スポンサー/協力者

場所

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