Cytokine Storm, SARS-CoV-2
Conditions
Keywords
Doxycycline, Cytokine Storm, SARS-CoV-2
Brief 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.
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.
Interventions
DRUGDoxycycline
100 MG Tablet
DRUGPlacebo
Placebo Tablet
Sponsors
Temple University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
This study will randomize 20 patients with confirmed or highly suspected early stage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients to Doxycycline (100 mg BID) or Placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Free of Either Hospitalization, Hypoxemia, ICU Admission or Death | 21 days | Days Alive and Out of Hospital (Composite Endpoint) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SARS-CoV-2 Serum Quantitative Viral Load | 21 days | Change From Baseline of SARS-CoV-2 Serum Quantitative Viral Load |
| SARS-CoV-2 IgM/IgG Antibodies | 21 days | Change From Baseline of SARS-CoV-2 IgM/IgG Antibodies (Positive/Negative) |
| White Blood Cell Count (WBC) | 21 days | Change From Baseline of White Blood Count (CBC) K/mm3 |
| Absolute Lymphocyte Count (ALC) | 21 days | Change From Baseline of Absolute Lymphocyte Count (ALC) K/mm3 |
| C-Reactive Protein (CRP) | 21 days | Change From Baseline of C-Reactive Protein (CRP) mg/dL |
| NP SARS-CoV-2 PCR | 21 days | Change From Baseline of Nasopharyngeal Luminex NxTAG CoV (Positive/Negative) |
| High Sensitivity Troponin I (hsTnT) | 21 days | Change From Baseline of High Sensitivity Troponin I (hsTnT) ng/mL |
| Tumor Necrosis Factor Alpha (TNF-a) | 21 days | Change From Baseline of Tumor Necrosis Factor Alpha (TNF-a) |
| IL-1 | 21 days | Change From Baseline of IL-1 |
| IL-1B | 21 days | Change From Baseline of IL-1B |
| IL-6 | 21 days | Change From Baseline of IL-6 |
| N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP) | 21 days | Change From Baseline of N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP) pg/mL |
Countries
United States
Outcome results
None listed