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.
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.
Drug: Doxycycline
100 MG Tablet
Drug: Placebo
Placebo Tablet
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
Temple University Hospital
Philadelphia, Pennsylvania, United States
Arthur M Feldman, MD, PhD, Principal Investigator
Temple University