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Trial record 1 of 1 for:    NCT04326920
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Sargramostim in Patients With Acute Hypoxic Respiratory Failure Due to COVID-19 (SARPAC) (SARPAC)

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ClinicalTrials.gov Identifier: NCT04326920
Recruitment Status : Recruiting
First Posted : March 30, 2020
Last Update Posted : April 24, 2020
Sponsor:
Collaborator:
Flanders Institute of Biotechnology
Information provided by (Responsible Party):
Bart N. Lambrecht, University Hospital, Ghent

Tracking Information
First Submitted Date  ICMJE March 24, 2020
First Posted Date  ICMJE March 30, 2020
Last Update Posted Date April 24, 2020
Actual Study Start Date  ICMJE March 24, 2020
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
  • 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 [ Time Frame: during hospital admission (up to 28 days) ]
    demonstrated by bacterial or fungal culture
  • 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 [ Time Frame: at enrolment, end of 5 day treatment period, 10 day period, 10-20 weeks ]
    defined by HS (Hemophagocytic Syndrome) score
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sargramostim in Patients With Acute Hypoxic Respiratory Failure Due to COVID-19 (SARPAC)
Official Title  ICMJE 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.
Brief Summary 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.
Detailed Description

Leukine® is a yeast-derived recombinant humanized granulocyte-macrophage colony stimulating factor (rhuGM-CSF, sargramostim) and the only FDA approved GM-CSF. GMCSF, a pleiotropic cytokine, is an important leukocyte growth factor known to play a key role in hematopoiesis, effecting the growth and maturation of multiple cell lineages as well as the functional activities of these cells in antigen presentation and cell mediated immunity.

Leukine inhalation or intravenous administration, as an adjuvant therapy, may confer benefit to patients with ARDS (Acute Respiratory Distress Syndrome) due to COVID-19 exposure, who are at significant risk of mortality. While there is no active IND (Investigational New Drug) for Leukine in the proposed patient population, Leukine is being studied in Fase II as an adjuvant therapy in the management of life-threatening infections to boost the hosts innate immune response to fight infection, reduce the risk of secondary infection, and in varied conditions as prevention of infection during critical illness. Inhaled Leukine has also been successfully used as primary therapy to improve oxygenation in patients with disordered gas exchange in the lungs. We propose that based on preclinical and clinical data, Leukine inhalation, as an adjuvant therapy, has an acceptable benefit-risk for use in patients with hypoxic respiratory failure and ARDS due to COVID-19 exposure, who are at significant risk of mortality.

Confirmed COVID19 patients with hypoxic respiratory failure (saturation below 93% on minimal 2 l/min O2) will be randomized to receive sargramostim 125mcg twice daily for 5 days as a nebulized inhalation on top of standard of care, or to receive standard of care treatment. Upon progression of disease requiring initiation of mechanical ventilatory support within the 5 day period, in patients in the active group, inhaled sargramostim will be replaced by intravenous sargramostim 125mcg/m2 body surface area 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. In the control group progressive desease requiring mechanical ventilatory support, from day 6 onwards, the treating physician will have the option to initiate IV sargramostim 125mcg/m2 body surface area for 5 days. Safety data, including blood leukocyte counts, will be collected in all patients. Efficacy data will also be collected and will include arterial blood gases, oxygenation parameters, need for ventilation, lung compliance, organ function, radiographic changes, ferritin levels, etc. as well as occurrence of secondary bacterial infections.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: Sargramostim
    Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration
    Other Name: LEUKINE
  • Other: Control
    Standard of care
Study Arms  ICMJE
  • Active Comparator: 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
    Intervention: Drug: Sargramostim
  • Placebo Comparator: 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
    Interventions:
    • Drug: Sargramostim
    • Other: Control
Publications * Bosteels C, Maes B, Van Damme K, De Leeuw E, Declercq J, Delporte A, Demeyere B, Vermeersch S, Vuylsteke M, Willaert J, Bollé L, Vanbiervliet Y, Decuypere J, Libeer F, Vandecasteele S, Peene I, Lambrecht B. Sargramostim to treat patients with acute hypoxic respiratory failure due to COVID-19 (SARPAC): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 5;21(1):491. doi: 10.1186/s13063-020-04451-7. Erratum in: Trials. 2020 Jun 22;21(1):554.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 27, 2020)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anja Delporte +32-9-3320228 anja.delporte@uzgent.be
Contact: Bart Lambrecht, MD PhD +32-9-3329110 bart.lambrecht@ugent.be
Listed Location Countries  ICMJE Belgium
Removed Location Countries Italy
 
Administrative Information
NCT Number  ICMJE NCT04326920
Other Study ID Numbers  ICMJE SARPAC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bart N. Lambrecht, University Hospital, Ghent
Study Sponsor  ICMJE University Hospital, Ghent
Collaborators  ICMJE Flanders Institute of Biotechnology
Investigators  ICMJE
Principal Investigator: Bart Lambrecht University Hospital, Ghent
PRS Account University Hospital, Ghent
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP