Either you have JavaScript disabled or your browser does not support Javascript . To work properly, this page requires JavaScript to be enabled.
How to enable JavaScript in your browser?

A Prospective, Randomized, Open-label, Interventional Study to Investigate the Efficacy of Sargramostim (Leukine) in Improving Oxygenation and Short- and Long-term Outcome of COVID-19 (Corona Virus Disease) Patients With Acute Hypoxic Respiratory Failure.

Trial Profile

A Prospective, Randomized, Open-label, Interventional Study to Investigate the Efficacy of Sargramostim (Leukine) in Improving Oxygenation and Short- and Long-term Outcome of COVID-19 (Corona Virus Disease) Patients With Acute Hypoxic Respiratory Failure.

Status: Recruiting
Phase of Trial: Phase IV

Latest Information Update: 28 May 2020

At a glance

  • Drugs Sargramostim (Primary) ; Sargramostim (Primary)
  • Indications Acute hypoxia; COVID 2019 infections; Hypoxaemia; Respiratory insufficiency
  • Focus Pharmacodynamics; Therapeutic Use
  • Acronyms SARPAC
  • Most Recent Events

    • 28 May 2020 According to an Partner Therapeutics media release, this study is nearing completion.
    • 27 Mar 2020 New trial record
    • 24 Mar 2020 According to a Partner Therapeutics media release, the SARPAC trial initiated at the University Hospital Ghent in Belgium. Bart Lambrecht is a Principal Investigator for the trial at University Hospital Ghent and the Flanders Institute of Biotechnology.

Trial Overview

Purpose

Phase IV study to evaluate the effectiveness of additional inhaled sargramostim (GM-CSF) versus standard of care on blood oxygenation in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure.

Primary Endpoints

To measure the effectiveness of sargramostim on restoring lung homeostasis

the primary endpoint of this intervention is measuring oxygenation after 5 DAYS of inhaled (and intraveneous) treatment through assessment of pretreatment (day 0) and post-treatment (day 5) ratio of PaO2/FiO2 and through measurement of the P(A-a)O2 gradient, which can easily be performed in the setting of clinical observation of patients admitted to the COVID -19 ward or ICU COVID-19 unit. During the 5 day treatment period, we will perform daily measurements of oxygen saturation (pulse oxymetry) in relation to FiO2, and the slope of alterations in this parameters could also be an indicator that our hypothesis is correct.
Timepoint: day 5

Improvement in oxygenation at a dose of 250 mcg daily during 5 days improves oxygenation in COVID-19 patients with acute hypoxic respiratory failure

[ Time Frame: at end of 5 day treatment period ]
by mean change in PaO2/FiO2 (PaO2=Partial pressure of oxygen; FiO2= Fraction of inspired oxygen)

Other Endpoints

Incidence of AE (Adverse Event)

time_frame: at end of 5 day treatment period, 10 day period, 10-20 weeks

Incidence of SAEs (Serious Adverse Event)

time_frame: at end of 5 day treatment period, 10 day period, 10-20 weeks

Clinical Status using 6-point ordinal scale

time_frame: at end of 5 day treatment period, 10 day period, 10-20 weeks

Clinical Status using Clincal sign score

time_frame: at end of 5 day treatment period, 10 day period,10-20 weeks

Clinical Status using SOFA score (Sequential Organ Failure Assessment score),

time_frame: at end of 5 day treatment period, 10 day period, 10-20 weeks

Clinical Status using NEWS2 score (National Early Warning Score)

time_frame: at end of 5 day treatment period, 10 day period, 10-20 weeks

incidence of severe or life-threatening bacterial, invasive fungal or opportunistic infection

description: demonstrated by bacterial or fungal culture
time_frame: during hospital admission (up to 28 days)

number of patients requiring initiation of mechanical ventilation

time_frame: during hospital admission (up to 28 days)

Number of deaths due to any cause at 4 weeks

time_frame: 4 weeks post inclusion

Number of deaths due to any cause at 20 weeks

time_frame: 20 weeks post inclusion

number of patients developing features of secondary haemophagocytic lymphohistiocytosis

description: defined by HS (Hemophagocytic Syndrome) score
time_frame: at enrolment, end of 5 day treatment period, 10 day period, 10-20 weeks

long term Clinical status defined by 6-point ordinal scale

time_frame: 10-20 week

long term Clinical status defined by chest X-ray

time_frame: 10-20 weeks

long term Clinical status defined lung function

time_frame: 10-12 weeks [1]

Diseases Treated

Indication Qualifiers Patient Segments
Acute hypoxia treatment -
COVID 2019 infections treatment -
Hypoxaemia treatment -
Respiratory insufficiency treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 80

  • Sex male & female
  • Age Group 18-80 years; adult; elderly

Patient Inclusion Criteria

- Recent (≤2weeks prior to Randomization) confident diagnosis of COVID-19 confirmed by antigen detection and/or PCR (Polymerase Chain Reaction), and/or seroconversion or any other emerging and validated diagnostic test - In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), a patient can be enrolled as probable COVID-19 infected. In all cases, this needs confirmation by later seroconversion. - Presence of acute hypoxic respiratory failure defined as (either or both) - saturation below 93% on minimal 2 l/min O2 - PaO2/FiO2 below 300 - Admitted to specialized COVID-19 ward - Age 18-80 - Male or Female - Willing to provide informed consent

Patient Exclusion Criteria

- Patients with known history of serious allergic reactions, including anaphylaxis, to human granulocyte-macrophage colony stimulating factor such as sargramostim, yeast-derived products, or any component of the product.- mechanical ventilation before start of study- patients with peripheral white blood cell count above 25.000 per microliter and/or active myeloid malignancy-patients on high dose systemic steroids (> 20 mg methylprednisolone or equivalent)-patients on lithium carbonate therapy- Patients enrolled in another investigational drug study- Pregnant or breastfeeding females (all female subjects regardless of childbearing potential status must have negative pregnancy test at screening)- Patients with serum ferritin >2000 mcg/ml (which will exclude ongoing HLH)

Trial Details

Identifiers

Identifier Owner
NCT04326920 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001254-22 European Clinical Trials Database
SARPAC -

Organisations

  • Affiliations Partner Therapeutics; Tanner Pharma Group

Trial Dates

  • Initiation Dates

    Actual : 24 Mar 2020

  • Primary Completion Dates

    Planned : 31 Oct 2020

  • End Dates

    Planned : 31 Dec 2020

Other Details

  • Design multicentre; open; parallel; prospective; randomised
  • Phase of Trial Phase IV
  • Location Belgium; Germany; Italy; Spain
  • Focus Pharmacodynamics; Therapeutic Use

Interventions

Drugs Route Formulation
SargramostimPrimary Drug Inhalation Solution
SargramostimPrimary Drug Intravenous Infusion

Active sargramostim treatment group

Inhaled sargramostim 125mcg twice daily for 5 days on top of standard of care. Upon progression to ARDS and initiation of mechanical ventilator support within the 5 day period, inhaled sargramostim will be replaced by intravenous sargramostim 125mcg/m2 body surface area once daily until the 5 day period is reached. From day 6 onwards, progressive patients in the active group will have the option to receive an additional 5 days of IV sargramostim, based on the treating physician's assessment
Drug: Sargramostim (Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration) Other Name: LEUKINE

Control group

standard of care. Subjects progressing to ARDS and requiring invasive mechanical ventilatory support, from day 6 onwards, will have the option (clinician's decision) to initiate IV sargramostim 125mcg/m2 body surface area once daily for 5 days
Drug: Sargramostim (Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration) Other Name: LEUKINE
Other: Control (Standard of care)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Anja Delporte
+32-9-3320228
anja.delporte@uzgent.be
show details
, University Hospital Ghent Belgium
Bart Lambrecht, MD PhD
+32-9-3329110
bart.lambrecht@ugent.be
show details
University Hospital Ghent, University Hospital, Ghent Belgium
HIRUZ CTU
C. Heymanslaan 10
Ghent
Postcode: 9000
Belgium
Telephone: +3293320500
Fax: +3293320520
hiruz.ctu@uzgent.be
show details
University Hospital Ghent Belgium
Ingel Demedts, MD PhD
ingel.demedts@azdelta.be
show details
AZ Delta Roeselare Belgium
Sabine Allard, MD PhD
sabine.allard@uzbrussel.be
show details
UZ Brussel Belgium
Stefaan Vandecasteele, MD Phd
+32-50 45 23 10 stefaan.vandecasteele@azsintjan.be
show details
AZ Sint Jan Brugge Belgium

Centres

Centre Name Location Trial Centre Country
-
-
-
AZ Delta Roeselare Roeselare Belgium
AZ Sint Jan Brugge Brugge Belgium
Flanders Institute of Biotechnology
-
-
University Hospital Ghent
-
-
University Hospital Ghent Ghent Belgium
University Hospital Ghent Gent Belgium
University Hospital, Ghent
-
-
UZ Brussel Jette Belgium

Trial History

Event Date Event Type Comment
28 May 2020 Other trial event According to an Partner Therapeutics media release, this study is nearing completion. Updated 02 Jun 2020
27 Apr 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 27 Apr 2020
19 Apr 2020 Other trial event Last checked against European Clinical Trials Database record. Updated 19 Apr 2020
02 Apr 2020 Other trial event New source identified and integrated (ClinicalTrials.gov: US National Institutes of Health: NCT04326920) Updated 02 Apr 2020
30 Mar 2020 Other trial event New source identified and integrated (European Clinical Trials Database;EudraCT2020-001254-22) Updated 30 Mar 2020
27 Mar 2020 New trial record New trial record Updated 27 Mar 2020
24 Mar 2020 Other trial event According to a Partner Therapeutics media release, the SARPAC trial initiated at the University Hospital Ghent in Belgium. Bart Lambrecht is a Principal Investigator for the trial at University Hospital Ghent and the Flanders Institute of Biotechnology. Updated 27 Mar 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  3. Partner Therapeutics. Partner Therapeutics Announces Initiation of Clinical Trial to Evaluate Leukine(Rm) in Patients with COVID-19 Associated Respiratory Illness. Media-Rel 2020;.

    Media Release
  4. Partner Therapeutics. Partner Therapeutics Announces Initiation of Clinical Trial to Evaluate Leukine(Rm) in Respiratory Illness in Patients with COVID-19 at Singapore General Hospital. Media-Rel 2020;.

    Media Release
Back to top