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

SARS-CoV-2 Clinical Trial

— STORM  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04433078
• Other study ID #: The STORM Trial
• Status: Withdrawn
• Phase: Phase 2
• Start date: June 22, 2020
• Est. completion date: April 13, 2021

Study information

• Verified date: April 2021
• Source: Temple University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 13, 2021
• Est. primary completion date: April 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cytokine Storm
• SARS-CoV-2

Intervention

Drug:
• Doxycycline
100 MG Tablet
• Placebo
Placebo Tablet

Locations

Country	Name	City	State
United States	Temple University Hospital	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Temple University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time Free of Either Hospitalization, Hypoxemia, ICU Admission or Death	Days Alive and Out of Hospital (Composite Endpoint)	21 days
Secondary	NP SARS-CoV-2 PCR	Change From Baseline of Nasopharyngeal Luminex NxTAG CoV (Positive/Negative)	21 days
Secondary	SARS-CoV-2 Serum Quantitative Viral Load	Change From Baseline of SARS-CoV-2 Serum Quantitative Viral Load	21 days
Secondary	SARS-CoV-2 IgM/IgG Antibodies	Change From Baseline of SARS-CoV-2 IgM/IgG Antibodies (Positive/Negative)	21 days
Secondary	White Blood Cell Count (WBC)	Change From Baseline of White Blood Count (CBC) K/mm3	21 days
Secondary	Absolute Lymphocyte Count (ALC)	Change From Baseline of Absolute Lymphocyte Count (ALC) K/mm3	21 days
Secondary	C-Reactive Protein (CRP)	Change From Baseline of C-Reactive Protein (CRP) mg/dL	21 days
Secondary	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
Secondary	High Sensitivity Troponin I (hsTnT)	Change From Baseline of High Sensitivity Troponin I (hsTnT) ng/mL	21 days
Secondary	Tumor Necrosis Factor Alpha (TNF-a)	Change From Baseline of Tumor Necrosis Factor Alpha (TNF-a)	21 days
Secondary	IL-1	Change From Baseline of IL-1	21 days
Secondary	IL-1B	Change From Baseline of IL-1B	21 days
Secondary	IL-6	Change From Baseline of IL-6	21 days