Enriched Heparin Anti COVID-19 Trial

NCT04743011 | Completed Phase 1 Results DMC

• 1 other identifier: UPECLIN-MB-2
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Covid19

Keywords

COVID-19; Heparin; Antiviral Agents; Blood Coagulation; Clinical Protocols

Outcome Measures

Primary Outcomes (2)

• Change in Activated Partial Thromboplastin Time (APTT) > 1.5 Seconds

  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 APTT ratio \> 1.5 or heparin-induced thrombocytopenia. In Brazilian standards, the APTT is measured in seconds and compared to a laboratory control for a ratio, which is used as a measurement.

  Immediately or up to 8 days after starting treatment

• Number of Participants With a Negative Viral Load in Nasal Swab Reverse Transcription Polymerase Chain Reaction (RT-PCR).

  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. The measurement consists in patients that tested negative for any viral load at the end of the treatment.

  Immediately or up to 8 days after starting treatment

Secondary Outcomes (8)

• Number of Participants That Develop Renal Failure

  Immediately or up to 8 days after starting treatment

• Number of Participants That Develop Major Cardiovascular Events

  Immediately or up to 8 days after starting treatment

• Number of Participants That Develop Deep Vein Thrombosis (DVT)

  Immediately or up to 8 days after starting treatment

• Number of Participants That Develop Pancreatitis

  Immediately or up to 8 days after starting treatment

• Number of Deaths Among Participants

  Immediately or up to 8 days after starting treatment

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses).

Drug: Placebo

Heparin sodium

ACTIVE COMPARATOR

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).

Drug: Heparin sodium

Interventions

Heparin sodium DRUG

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)

Also known as: Hepamax S BLAU

Heparin sodium

Placebo DRUG

Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)

Also known as: Saline solution 0.9%, Physiological solution 0.9%

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Need for supplemental oxygen therapy (O2) less than 5L / min.

You may not qualify if:

• 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;

Sponsors & Collaborators

• UPECLIN HC FM Botucatu Unesp: lead

Study Sites (2)

School of Medicine at Botucatu- Paulista State University- UNESP, São Paulo, Brazil

Botucatu, São Paulo, 18607030, Brazil

Location

Hospital das Clinicas de Boucatu

Botucatu, São Paulo, 18618970, Brazil

Location

Related Publications (2)

• Phelps MK, Olson LM, Patel MAVB, Thompson MJ, Murphy CV. Nebulized Heparin for Adult Patients With Smoke Inhalation Injury: A Review of the Literature. J Pharm Technol. 2020 Aug;36(4):130-140. doi: 10.1177/8755122520925774. Epub 2020 Jun 1.

  PMID: 34752548 BACKGROUND

• Ramos da Silva Grillo VT, Bertanha M, da Silva Rodrigues L, de Lima MA, Mellucci Filho PL, Rahal Guaragna Machado R, Durigon EL, Dias Sertorio N, de Assis Golim M, Moroz A, Marques Braz AM, de Moraes LN, Leite MA, Bonciani Nader H, de Campos GC, Rodrigues Guzzo Carvalho C, Florenca Cardoso F, Magro AJ, Caputo Nunes H, Tommasini Grotto RM, de Cassia Alvarado R, de Moura Campos Pardini MI, Lima Sobreira M, da Costa EAPN, Naime Barbosa A, Fortaleza CMCB. Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial. Sci Rep. 2024 Aug 27;14(1):19902. doi: 10.1038/s41598-024-70064-8.

  PMID: 39191809 DERIVED

MeSH Terms

Conditions

COVID-19; Thrombosis

Interventions

Heparin; Saline Solution

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Professor Matheus Bertanha, Ph.D.
• Organization: São Paulo State University (UNESP)

matheusbertanha@gmail.com

+551438801444

Study Officials

• Matheus Bertanha, PhD

  São Paulo State University (Unesp)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The clinical trial will be triple-blind. Participants, researchers, and the data/statistical analysis team will not have access to the research data. Only one member of the team will produce the test product and assist a external physician (not part of the research team), with the adverse events that may occur with the participants during the execution of the research.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants allocated to Group 1 (control) will receive inhalation with 0.9% saline solution applied 4/4 hours, for 7 days. Participants allocated to Group 2 (intervention) will receive high molecular weight inhaled heparin (2,5mg / mL 0.9% SF), at a 4/4 hour dose, for 7 days.

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: February 8, 2021
• Study Start: June 1, 2021
• Primary Completion: November 30, 2021
• Study Completion: December 31, 2021
• Last Updated: October 15, 2024
• Results First Posted: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The summary data will be published or made available 6 months after publication.
• Access Criteria: 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.

Locations

BR (2)