RepurpoSing Old Drugs TO SuppRess a Modern Threat: COVID-19 STORM (STORM)

RepurpoSing Old Drugs TO SuppRess a Modern Threat: The STORM Trial

The primary aim of this study is to test whether Doxycycline can benefit patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections by inhibiting the replication of the virus while at the same time blocking the development of cytokine storms or inhibiting cytokine-associated coagulopathy respectively. The investigators hypothesize that Doxycycline will will improve survival and reduce morbidity in SARS-CoV-2 infected patients.

A secondary aim is to identify genetic variants that predict either an unusually mild disease or an unusually severe disease - knowledge that can be used to design new and precise medications and to be able to predict patients who might get into early trouble and to therefore hospitalize them.

Study Overview

• Status: Withdrawn
• Conditions: SARS-CoV-2; Cytokine Storm
• Intervention / Treatment: Drug: Placebo; Drug: Doxycycline

Detailed Description

This study will randomize 20 patients with confirmed or highly suspected early stage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to Doxycycline (100 mg BID) or Placebo and then assess the progression of their disease over the next three weeks with the primary endpoint being days alive and out of the hospital.

The investigators will collect specimens for measurement of viral burden (nasopharyngeal luminex (SARS-CoV-2), SARS-CoV-2 serum quantitative viral load, SARS-CoV-2 IgM/IgG antibodies), markers of inflammation (WBC, ESR, TNFa, IL-1, IL-6, IL-1B), and cardiac dysfunction (CRP, pro-BNP, hsTnT).

Eligibility will be based on history and physical examination findings - collated into a clinical suspicion score. The decision to enroll based on clinical suspicion score rather than confirmed SARS-CoV-2 disease is based on the variable and unacceptably high false negative rate of the nasopharyngeal PCR test for in early disease.

Clinical Suspicion Score: Greater than or equal to 6/20 (at least 4 points of which must be clinical) will be eligible for enrollment.

Clinical Criteria: Max 12 points

• Fever (2 points)
• Cough (2 points)
• Dyspnea (2 points)
• Chest pain (1 point)
• Myalgias (1 point)
• Fatigue (1 point)
• GI symptoms (1 point)
• Loss of Smell (1 point)
• Loss of Taste (1 point)

Exposure Criteria: Max 8 points

• Contact with known COVID+ (2 points)
• Healthcare worker -- frequent <6 feet contact for 15 minutes (2 points)
• High-risk work -- supermarket, deli, transportation (2 points)
• Endemic community -- prison/jail/nursing home/LTAC/SNF/rehab/homeless/homeless shelter (2 points)

Genetic variants may explain why patients who are infected with SARS-CoV-2 have either a relatively benign or an inappropriately aggressive response to an infectious insult. Medications may be more or less effective in that group of patients harboring genetic variants of a disease-related protein. To better understand this, whole genome sequencing and analysis will be performed on all study patients.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed or highly suspected early stage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disease with clinical suspicion score >6/20, not requiring hospitalization
• Age ≥18 years
• Willing to sign the informed consent form
• Willing to take study drug or placebo as directed for 21 days

Exclusion Criteria:

• Confirmed or highly suspected early stage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disease with clinical suspicion score >6/20, requiring hospitalization
• Suspected or confirmed convalescent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), within the prior 4 weeks
• Age <18 years' old
• Inability to take medications orally
• Inability to provide written consent
• Known sensitivity/allergy to doxycycline or tetracyclines
• Current use of doxycycline for another indication
• Pregnancy
• A known diagnosis of myasthenia gravis
• History of Clostridium Difficile infection within past 12 months
• Sun sensitivity
• Individuals using medications which could lower doxycycline levels, including barbiturates, phenytoin, carbamazepine, warfarin
• Individuals using isotretinoin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxycycline; Participants receive 100 MG BID for 21 days	Drug: Doxycycline; 100 MG Tablet
Placebo Comparator: Placebo; Participants receive Placebo BID for 21 days	Drug: Placebo; Placebo Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Free of Either Hospitalization, Hypoxemia, ICU Admission or Death	Days Alive and Out of Hospital (Composite Endpoint)	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NP SARS-CoV-2 PCR	Change From Baseline of Nasopharyngeal Luminex NxTAG CoV (Positive/Negative)	21 days
SARS-CoV-2 Serum Quantitative Viral Load	Change From Baseline of SARS-CoV-2 Serum Quantitative Viral Load	21 days
SARS-CoV-2 IgM/IgG Antibodies	Change From Baseline of SARS-CoV-2 IgM/IgG Antibodies (Positive/Negative)	21 days
White Blood Cell Count (WBC)	Change From Baseline of White Blood Count (CBC) K/mm3	21 days
Absolute Lymphocyte Count (ALC)	Change From Baseline of Absolute Lymphocyte Count (ALC) K/mm3	21 days
C-Reactive Protein (CRP)	Change From Baseline of C-Reactive Protein (CRP) mg/dL	21 days
N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP)	Change From Baseline of N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP) pg/mL	21 days
High Sensitivity Troponin I (hsTnT)	Change From Baseline of High Sensitivity Troponin I (hsTnT) ng/mL	21 days
Tumor Necrosis Factor Alpha (TNF-a)	Change From Baseline of Tumor Necrosis Factor Alpha (TNF-a)	21 days
IL-1	Change From Baseline of IL-1	21 days
IL-1B	Change From Baseline of IL-1B	21 days
IL-6	Change From Baseline of IL-6	21 days

Collaborators and Investigators

• Sponsor: Temple University
• Investigators: Principal Investigator: Arthur M Feldman, MD, PhD, Temple University

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2020
• Primary Completion (Actual): April 13, 2021
• Study Completion (Actual): April 13, 2021

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: April 13, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Doxycycline; Cytokine Storm
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Cytokine Release Syndrome; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: The STORM Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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.: No