NCT04661930

Brief Summary

This is an open-label run-in followed by a randomized, double-blind drug treatment study of COVID-19 infected patients requiring inpatient hospital admission.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
55

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jan 2021

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 9, 2020

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 10, 2020

Completed
22 days until next milestone

Study Start

First participant enrolled

January 1, 2021

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2022

Completed
Last Updated

April 19, 2022

Status Verified

April 1, 2022

Enrollment Period

1.3 years

First QC Date

December 9, 2020

Last Update Submit

April 17, 2022

Conditions

Outcome Measures

Primary Outcomes (12)

  • Number of Therapeutic Oxygen-Free Days

    Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.

    14 days

  • Length of Hospital Stay

    Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm

    14 days

  • Viral Clearance by Nasopharyngeal Swab

    Nasopharyngeal swabs will be collected every second day for the duration of study participation. Viral clearance is measured as fold change in viral genetic copies per mL

    14 days

  • Difference in Estimated P/F Ratio at 14 days

    Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available.

    14 days

  • Difference in Plasma Neutrophils at 14 days

    Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.

    14 days

  • Difference in Plasma Lymphocytes at 14 days

    Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.

    14 days

  • Difference in Plasma Monocytes at 14 days

    Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.

    14 days

  • Difference in Plasma C-Reactive Protein (CRP) at 14 days

    Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.

    14 days

  • Difference in Plasma IL-6 at 14 days

    Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.

    14 days

  • Difference in Plasma Procalcitonin (PCT) at 14 days

    Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.

    14 days

  • Difference in Plasma Ferritin at 14 days

    Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.

    14 days

  • Difference in NLR (Neutrophils to Lymphocytes Ratio) at 14 days

    Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.

    14 days

Secondary Outcomes (59)

  • 14-Day Mortality

    14 days

  • Difference in Organ Injury Plasma markers at 14 days - Lactate

    14 days

  • Difference in Organ Injury Plasma markers at 14 days - Cardiac Troponin (TRO)

    14 days

  • Difference in Organ Injury Plasma markers at 14 days - Creatine Kinase (CK)

    14 days

  • Difference in Organ Injury Plasma markers at 14 days - Alanine Aminotransferase (ALT)

    14 days

  • +54 more secondary outcomes

Other Outcomes (3)

  • Significant post-acute incident diagnoses after recovery at 28-days

    1 day

  • Significant post-acute incident diagnoses after recovery at 90-days

    1 day

  • Significant post-acute incident diagnoses after recovery at 6-months

    1 day

Study Arms (3)

Fenofibrate + Usual Care

EXPERIMENTAL

Participants in this arm will receive the study drug, Fenofibrate, in combination with usual care.

Drug: TriCor® 145mg tabletsOther: Usual care

Placebo + Usual Care

PLACEBO COMPARATOR

Participants in this arm will receive placebo treatment, in combination with usual care.

Other: PlaceboOther: Usual care

Usual Care (Observetional)

NO INTERVENTION

Participants in this arm will receive the usual care and be compared by their medical records and laboratory results

Interventions

Fenofibrate; 145 mg daily (1/day); oral administration; 10 days

Also known as: Lipanthyl NT 145mg tablets
Fenofibrate + Usual Care
PlaceboOTHER

Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration

Placebo + Usual Care

All participants will otherwise receive usual medical care

Fenofibrate + Usual CarePlacebo + Usual Care

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Presumptive positive laboratory test for SARS-CoV-2 based on local laboratory standard
  • Age greater than or equal to 18 years of age
  • Severe COVID-19, defined by:
  • A disease severity score of 3 (Hospitalized, on non-invasive ventilation or high flow oxygen devices) to 4 (Hospitalized, requiring supplemental oxygen).
  • AND o A respiratory SOFA \>=1 and increased oxygen requirement compared to baseline among those on home O2, a blood oxygen saturation of 93% or less on room air, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) of less than 300 mm Hg, respiratory rate \>30 breaths/min, or lung infiltrates \>50% on chest CT
  • Enrollment within 72 hours of presentation of hospital admission or within 72 hours of a positive test result, whichever is later

You may not qualify if:

  • Enrollment \> 72 hours of admission order or positive test result, whichever is later
  • Admission to the hospital with a respiratory SOFA \>=5 , Critical COVID-19, or Disease Severity Score \>5 (requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or all)
  • Known hypersensitivity to fenofibrate
  • For female subjects:
  • Pregenant, determined by a human chorionic gonadotropin (HCG) rapid detection kit or a blood test
  • Breastfeeding
  • Undergoing fertility treatments
  • Patient-reported history or electronic medical record history of kidney disease, defined as:
  • Any history of dialysis
  • History of chronic kidney disease stage IV
  • Estimated Glomerular Filtration Rate (eGFR) of \< 30ml/min/1.73 m2 at the time of enrollment
  • Acute pre-renal azotemia at the time of enrollment in the opinion of the investigator or bedside clinician
  • Most recent mean arterial blood pressure prior to enrollment \<65 mmHg
  • Patient-reported history or electronic medical record history of severe liver disease, defined as:
  • Cirrhosis
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Barzilai Medical Center

Ashkelon, 7830604, Israel

RECRUITING

Rambam Health Care Campus

Haifa, Israel

RECRUITING

Nazareth Hospital EMMS

Nazareth, Israel

RECRUITING

Related Publications (9)

  • Bornstein SR, Dalan R, Hopkins D, Mingrone G, Boehm BO. Endocrine and metabolic link to coronavirus infection. Nat Rev Endocrinol. 2020 Jun;16(6):297-298. doi: 10.1038/s41574-020-0353-9.

    PMID: 32242089BACKGROUND
  • Ehrlich, A., Uhl, S., Ioannidis, K., Hofree, M., tenOever, B., and Nahmias, Y. (2020). The SARS-CoV-2 Transcriptional Metabolic Signature in Lung Epithelium. SSRN Electronic Journal.

    BACKGROUND
  • McBride CE, Machamer CE. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein. Virology. 2010 Sep 15;405(1):139-48. doi: 10.1016/j.virol.2010.05.031. Epub 2010 Jul 1.

    PMID: 20580052BACKGROUND
  • Wu Q, Zhou L, Sun X, Yan Z, Hu C, Wu J, Xu L, Li X, Liu H, Yin P, Li K, Zhao J, Li Y, Wang X, Li Y, Zhang Q, Xu G, Chen H. Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection. Sci Rep. 2017 Aug 22;7(1):9110. doi: 10.1038/s41598-017-09536-z.

    PMID: 28831119BACKGROUND
  • Yan B, Chu H, Yang D, Sze KH, Lai PM, Yuan S, Shuai H, Wang Y, Kao RY, Chan JF, Yuen KY. Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication. Viruses. 2019 Jan 16;11(1):73. doi: 10.3390/v11010073.

    PMID: 30654597BACKGROUND
  • Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010 Sep;47(3):193-9. doi: 10.1007/s00592-009-0109-4. Epub 2009 Mar 31.

    PMID: 19333547BACKGROUND
  • Yuan S, Chu H, Chan JF, Ye ZW, Wen L, Yan B, Lai PM, Tee KM, Huang J, Chen D, Li C, Zhao X, Yang D, Chiu MC, Yip C, Poon VK, Chan CC, Sze KH, Zhou J, Chan IH, Kok KH, To KK, Kao RY, Lau JY, Jin DY, Perlman S, Yuen KY. SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target. Nat Commun. 2019 Jan 10;10(1):120. doi: 10.1038/s41467-018-08015-x.

    PMID: 30631056BACKGROUND
  • Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, Lei F, Wang H, Xie J, Wang W, Li H, Zhang P, Song X, Chen X, Xiang M, Zhang C, Bai L, Xiang D, Chen MM, Liu Y, Yan Y, Liu M, Mao W, Zou J, Liu L, Chen G, Luo P, Xiao B, Zhang C, Zhang Z, Lu Z, Wang J, Lu H, Xia X, Wang D, Liao X, Peng G, Ye P, Yang J, Yuan Y, Huang X, Guo J, Zhang BH, Li H. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metab. 2020 Jun 2;31(6):1068-1077.e3. doi: 10.1016/j.cmet.2020.04.021. Epub 2020 May 1.

    PMID: 32369736BACKGROUND
  • Ehrlich A, Ioannidis K, Nasar M, Abu Alkian I, Daskal Y, Atari N, Kliker L, Rainy N, Hofree M, Shafran Tikva S, Houri I, Cicero A, Pavanello C, Sirtori CR, Cohen JB, Chirinos JA, Deutsch L, Cohen M, Gottlieb A, Bar-Chaim A, Shibolet O, Mandelboim M, Maayan SL, Nahmias Y. Efficacy and safety of metabolic interventions for the treatment of severe COVID-19: in vitro, observational, and non-randomized open-label interventional study. Elife. 2023 Jan 27;12:e79946. doi: 10.7554/eLife.79946.

MeSH Terms

Conditions

COVID-19Respiratory Distress Syndrome

Interventions

Fenofibrate

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract DiseasesRespiration Disorders

Intervention Hierarchy (Ancestors)

Fibric AcidsIsobutyratesButyratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsPhenyl EthersEthersBenzophenonesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPhenolsKetones

Study Officials

  • Shlomo Mayaan, MD

    Barzilai Medical Center

    PRINCIPAL INVESTIGATOR
  • Mahram Nassar, MD

    Barzilai Medical Center

    STUDY DIRECTOR
  • Yaakov Nahmias, PhD

    Hebrew University of Jerusalem

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: An interventional single-arm non-randomized pilot study in 15 patients, followed by an Interventional double-blinded randomized quadruple masked study in 40 patients.
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Director of the Grass Center for Bioengineering

Study Record Dates

First Submitted

December 9, 2020

First Posted

December 10, 2020

Study Start

January 1, 2021

Primary Completion

May 1, 2022

Study Completion

July 1, 2022

Last Updated

April 19, 2022

Record last verified: 2022-04

Data Sharing

IPD Sharing
Will not share

Locations