Trial Outcomes & Findings for Enriched Heparin Anti COVID-19 Trial (NCT NCT04743011)

NCT ID: NCT04743011

Last Updated: 2024-10-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 27 participants
• Primary outcome timeframe: Immediately or up to 8 days after starting treatment
• Results posted on: 2024-10-15

Participant Flow

Participant milestones

Measure	Placebo Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	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). 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)
Overall Study STARTED	14	13
Overall Study COMPLETED	14	13
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Enriched Heparin Anti COVID-19 Trial

Baseline characteristics by cohort

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)	Total n=27 Participants Total of all reporting groups
Age, Continuous	52 years n=5 Participants	53 years n=7 Participants	53 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized White	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Weight	92 kilograms n=5 Participants	79 kilograms n=7 Participants	85 kilograms n=5 Participants
Height	168 centimeters n=5 Participants	162 centimeters n=7 Participants	165 centimeters n=5 Participants
Body Mass Index	33 kg/m² n=5 Participants	29.4 kg/m² n=7 Participants	31.3 kg/m² n=5 Participants
Hypertension	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Coronary Disease	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Dyslipidemia	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Sedentarism	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Tabagism	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Previous Tabagism (Ceased)	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Alcoholism	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Previous Stroke	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Previous Cancer	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Previous Transplantation or Immunosuppression	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Autoimmune Disease	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Pulmonary Emphysema or Asthma	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Hypothyroidism	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Anxiety or Depression Disorders	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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 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.

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Change in Activated Partial Thromboplastin Time (APTT) > 1.5 Seconds	0.95 ratio Interval 0.74 to 1.37	1.10 ratio Interval 0.88 to 1.45

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Number of Participants With a Negative Viral Load in Nasal Swab Reverse Transcription Polymerase Chain Reaction (RT-PCR).	8 Participants	8 Participants

SECONDARY outcome

Timeframe: Immediately or up to 8 days after starting treatment

Worsening of clinical parameters characterized by renal failure through measurement of urea and creatinine;

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Number of Participants That Develop Renal Failure	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Immediately or up to 8 days after starting treatment

Worsening of clinical parameters characterized by major cardiovascular events (pulmonary embolism, acute myocardial infarction)

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Number of Participants That Develop Major Cardiovascular Events	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Immediately or up to 8 days after starting treatment

Worsening of clinical parameters characterized by deep vein thrombosis (DVT);

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Number of Participants That Develop Deep Vein Thrombosis (DVT)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Immediately or up to 8 days after starting treatment

Worsening of clinical parameters characterized by pancreatitis through measurement of amylase (> 200 U/L);

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Number of Participants That Develop Pancreatitis	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Immediately or up to 8 days after starting treatment

Worsening of clinical parameters characterized by death;

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Number of Deaths Among Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Immediately or up to 8 days after starting treatment

Worsening of laboratory parameters measured by increase in C reactive protein test (>3.00mg/L);

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Number of Participants With Increased C Reactive Protein Test	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 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;

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Number of Participants With Deterioration of Arterial Blood Gas paO2/pFiO2 Ratio	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=14 Participants Participants will receive inhalation with 5mL 0.9% saline solution (placebo), 4/4h, during the day period (5 doses). Placebo: Nebulized inhalation of 5 mL of 0.9% saline solution, every 4 hours for 7 days, except during the nighttime (5 doses/day)	Heparin Sodium n=13 Participants 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). 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)
Number of Participants With Increased Pulmonary Area Compromised (%)	1 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Heparin Sodium

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Professor Matheus Bertanha, Ph.D.

São Paulo State University (UNESP)

Phone: +551438801444

Email: matheusbertanha@gmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place