Aprepitant Injectable Emulsion in Patients With COVID-19 (GUARDS-1)

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ClinicalTrials.gov Identifier: NCT04470622

Recruitment Status : Terminated (Study was terminated early by Heron, and was not terminated for safety reasons.)

First Posted : July 14, 2020

Results First Posted : August 30, 2022

Last Update Posted : August 30, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Heron Therapeutics

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	COVID-19
Interventions	Drug: Aprepitant injectable emulsion Drug: Saline Placebo
Enrollment	27

Participant Flow

Recruitment Details
Pre-assignment Details	One participant was prematurely randomized while failing screening eligibility. This subject was counted in both 'Screen Failures' and 'Randomized Subjects/ITT population', leading to a discrepancy between the Enrollment number in the Protocol Section (27) and the number of participants Started in the Participant Flow module (26).


Arm/Group Title	Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
Arm/Group Description	Aprepitant injectable emulsion, 130...	Saline Placebo, QD for 14 days.
Arm/Group Description	Aprepitant injectable emulsion, 130 mg once daily (QD) for 14 days.	Saline Placebo, QD for 14 days.
Period Title: Overall Study
Started	12	14
Completed	12	11
Not Completed	0	3
Reason Not Completed
Withdrawal by Subject	0	1
Screen Failure	0	1
Death	0	1

Baseline Characteristics

Arm/Group Title		Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo	Total
Arm/Group Description		Aprepitant injectable emulsion, 130...	Saline Placebo, QD for 14 days.	Total of all reporting groups
Arm/Group Description		Aprepitant injectable emulsion, 130 mg QD for 14 days.	Saline Placebo, QD for 14 days.	Total of all reporting groups
Overall Number of Baseline Participants		12	13	25
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Safety Population.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	12 participants	13 participants	25 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	6 50.0%	10 76.9%	16 64.0%
	>=65 years	6 50.0%	3 23.1%	9 36.0%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	12 participants	13 participants	25 participants
		61.8 (15.64)	57.7 (11.93)	59.7 (13.70)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	12 participants	13 participants	25 participants
	Female	6 50.0%	6 46.2%	12 48.0%
	Male	6 50.0%	7 53.8%	13 52.0%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	12 participants	13 participants	25 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	12 100.0%	13 100.0%	25 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	12 participants	13 participants	25 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 7.7%	1 4.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 8.3%	1 7.7%	2 8.0%
	White	11 91.7%	10 76.9%	21 84.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	1 7.7%	1 4.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	12 participants	13 participants	25 participants
United States		12	13	25

Outcome Measures

1.Primary Outcome


Title	Proportion of Subjects Alive and Discharged From the Hospital.
Description	ITT Population.
Description	ITT Population.
Time Frame	14 Days.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
Arm/Group Description:	Aprepitant injectable emulsion, 130...	Saline Placebo, QD for 14 days.
Arm/Group Description:	Aprepitant injectable emulsion, 130 mg QD for 14 days.	Saline Placebo, QD for 14 days.
Overall Number of Participants Analyzed	12	14
Measure Type: Count of Participants Unit of Measure: Participants
	11 91.7%	10 71.4%

2.Secondary Outcome


Title	Time to Death or Respiratory Failure, Defined as Any of the Following: Endotracheal Intubation and Mechanical Ventilation; Oxygen Delivered by High-flow Nasal Cannula; Noninvasive Positive Pressure Ventilation; Extracorporeal Membrane Oxygenation (ECMO).
Description	[Not Specified]
Description	[Not Specified]
Time Frame	56 Days.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
Arm/Group Description:	Aprepitant injectable emulsion, 130...	Saline Placebo, QD for 14 days.
Arm/Group Description:	Aprepitant injectable emulsion, 130 mg QD for 14 days.	Saline Placebo, QD for 14 days.
Overall Number of Participants Analyzed	12	14
Median (95% Confidence Interval) Unit of Measure: days
	NA ^[1] (2.00 to NA)	NA ^[1] (4.00 to NA)

[1]

The number of subjects with death or respiratory failure was too small to estimate the median

3.Secondary Outcome


Title	Time to Discharge From Hospital.
Description	[Not Specified]
Description	[Not Specified]
Time Frame	56 Days.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
Arm/Group Description:	Aprepitant injectable emulsion, 130...	Saline Placebo, QD for 14 days.
Arm/Group Description:	Aprepitant injectable emulsion, 130 mg QD for 14 days.	Saline Placebo, QD for 14 days.
Overall Number of Participants Analyzed	12	14
Median (95% Confidence Interval) Unit of Measure: days
	6.0 (3.00 to 8.00)	8.0 (4.00 to 11.00)

4.Secondary Outcome


Title	Change From Baseline in Interleukin 6 (IL-6).
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Days 7, 14, 28, Discharge (from 2 to 43 days; median 6 days (Aprepitant), 8 days (Placebo))

Outcome Measure Data

Analysis Population Description

Overall Number of Participants Analyzed reflects the Total Enrolled ITT Population whereas Number Analyzed in each row reflects the number of subjects with IL-6 data reported at the specified timepoint.


Arm/Group Title		Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
Arm/Group Description:		Aprepitant injectable emulsion, 130...	Saline Placebo, QD for 14 days.
Arm/Group Description:		Aprepitant injectable emulsion, 130 mg QD for 14 days.	Saline Placebo, QD for 14 days.
Overall Number of Participants Analyzed		12	14
Mean (Standard Deviation) Unit of Measure: pg/mL
Baseline	Number Analyzed	11 participants	12 participants
Baseline		18.77 (26.321)	19.11 (30.098)
Day 7	Number Analyzed	4 participants	8 participants
Day 7		-27.98 (42.493)	14.83 (65.384)
Day 14	Number Analyzed	1 participants	3 participants
Day 14		124.00 ^[1] (NA)	204.30 (407.244)
Day 28	Number Analyzed	1 participants	1 participants
Day 28		-8.00 ^[1] (NA)	2.90 ^[1] (NA)
Discharge	Number Analyzed	8 participants	6 participants
Discharge		-17.41 (30.754)	-9.68 (18.107)

[1]

The standard deviation is not defined when the sample size is equal to 1.

5.Secondary Outcome


Title	Incidence of Treatment-emergent Adverse Events.
Description	Number of subjects reporting at least on Treatment-Emergent Adverse Ev...
Description	Number of subjects reporting at least on Treatment-Emergent Adverse Event. Subjects reporting more than one event are counted only once using the highest severity.
Time Frame	Through Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
Arm/Group Description:	Aprepitant injectable emulsion, 130...	Saline Placebo, QD for 14 days.
Arm/Group Description:	Aprepitant injectable emulsion, 130 mg QD for 14 days.	Saline Placebo, QD for 14 days.
Overall Number of Participants Analyzed	12	13
Measure Type: Count of Participants Unit of Measure: Participants
	8 66.7%	5 38.5%

Adverse Events

Time Frame	Through Day 56.
Adverse Event Reporting Description	One subject was prematurely randomized while failing screening eligibility. This subject was counted in both 'Screen Failures' and 'Randomized Subjects/ITT population'. ITT Population includes all subjects who are randomized. Safety Population includes all subjects who received at least one dose of any study drug (including placebo). All-Cause Mortality was assessed in the ITT population. Serious and Other Adverse Events were assessed in the Safety Population.

Arm/Group Title	Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
Arm/Group Description	Aprepitant injectable emulsion, 130...	Saline Placebo, QD for 14 days.
Arm/Group Description	Aprepitant injectable emulsion, 130 mg QD for 14 days.	Saline Placebo, QD for 14 days.
All-Cause Mortality
	Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/12 (0.00%)	1/14 (7.14%)
Serious Adverse Events Serious Adverse Events
	Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/12 (16.67%)	2/13 (15.38%)
Blood and lymphatic system disorders
Blood loss anaemia ^† 1	0/12 (0.00%)	1/13 (7.69%)
Cardiac disorders
Sinus node dysfunction ^† 1	1/12 (8.33%)	0/13 (0.00%)
Injury, poisoning and procedural complications
Femur fracture ^† 1	1/12 (8.33%)	0/13 (0.00%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis ^† 1	0/12 (0.00%)	1/13 (7.69%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure ^† 1	1/12 (8.33%)	1/13 (7.69%)
1 Term from vocabulary, MedDRA, Version 23.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Treatment Group 1: Aprepitant Injectable Emulsion	Treatment Group 2: Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	8/12 (66.67%)	5/13 (38.46%)
Blood and lymphatic system disorders
Heparin-induced thrombocytopenia ^† 1	1/12 (8.33%)	0/13 (0.00%)
Anaemia ^† 1	0/12 (0.00%)	1/13 (7.69%)
Cardiac disorders
Atrial fibrillation ^† 1	1/12 (8.33%)	0/13 (0.00%)
Bradycardia ^† 1	1/12 (8.33%)	0/13 (0.00%)
Gastrointestinal disorders
Constipation ^† 1	2/12 (16.67%)	2/13 (15.38%)
Tongue discomfort ^† 1	1/12 (8.33%)	0/13 (0.00%)
Haemorrhoids ^† 1	0/12 (0.00%)	1/13 (7.69%)
Rectal haemorrhage ^† 1	0/12 (0.00%)	1/13 (7.69%)
General disorders
Non-cardiac chest pain ^† 1	1/12 (8.33%)	0/13 (0.00%)
Infections and infestations
Candida infection ^† 1	1/12 (8.33%)	0/13 (0.00%)
Leuconostoc infection ^† 1	0/12 (0.00%)	1/13 (7.69%)
Injury, poisoning and procedural complications
Anaemia postoperative ^* 1	1/12 (8.33%)	0/13 (0.00%)
Fall ^† 1	1/12 (8.33%)	0/13 (0.00%)
Investigations
Electrocardiogram QT prolonged ^† 1	1/12 (8.33%)	0/13 (0.00%)
Candida test positive ^† 1	0/12 (0.00%)	1/13 (7.69%)
Metabolism and nutrition disorders
Diabetes mellitus ^† 1	1/12 (8.33%)	1/13 (7.69%)
Hypernatraemia ^† 1	1/12 (8.33%)	1/13 (7.69%)
Hypocalcaemia ^† 1	0/12 (0.00%)	1/13 (7.69%)
Hypophosphataemia ^† 1	0/12 (0.00%)	1/13 (7.69%)
Musculoskeletal and connective tissue disorders
Haematoma muscle ^† 1	0/12 (0.00%)	1/13 (7.69%)
Pain in extremity ^† 1	0/12 (0.00%)	1/13 (7.69%)
Psychiatric disorders
Anxiety ^† 1	1/12 (8.33%)	1/13 (7.69%)
Confusional state ^† 1	1/12 (8.33%)	1/13 (7.69%)
Insomnia ^† 1	0/12 (0.00%)	1/13 (7.69%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure ^† 1	1/12 (8.33%)	1/13 (7.69%)
Pneumomediastinum ^† 1	1/12 (8.33%)	0/13 (0.00%)
Skin and subcutaneous tissue disorders
Rash ^† 1	1/12 (8.33%)	0/13 (0.00%)
Subcutaneous emphysema ^† 1	1/12 (8.33%)	0/13 (0.00%)
Vascular disorders
Hypertension ^† 1	1/12 (8.33%)	1/13 (7.69%)
1 Term from vocabulary, MedDRA, Version 23.0 † Indicates events were collected by systematic assessment * Indicates events were collected by non-systematic assessment

Limitations and Caveats

Study was terminated early by Heron, and was not terminated for safety reasons. The data reported is only safety data generated from the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Sophie Visonneau
Organization:	Heron Therapeutics, Inc.
Phone:	858-251-7232
EMail:	svisonneau@herontx.com

Layout table for additonal information

Responsible Party:	Heron Therapeutics
ClinicalTrials.gov Identifier:	NCT04470622
Other Study ID Numbers:	HTX-019-202
First Submitted:	July 13, 2020
First Posted:	July 14, 2020
Results First Submitted:	April 8, 2022
Results First Posted:	August 30, 2022
Last Update Posted:	August 30, 2022

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