Rural health systems can at times have less access to advanced clinical trials than do urban systems centering on prominent tertiary hospitals and academic medical centers. This is true during most times and perhaps even during the COVID-19 pandemic. A sort of divide exists between urban and rural centers when it comes to research. However, during the pandemic, the National Institutes of Health (NIH), particularly the National Institutes of Allergy and Infectious Diseases (NIAID), mobilized quickly to rationalize various investigational networks to focus on COVID-19 studies along with the formation of NIH Foundation’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), created to help guide which studies should receive federal research dollars from the Operation Warp Speed initiative formed by the previous POTUS. Apparently, New York State’s St. Lawrence Health System, in St. Lawrence County has gained as the system is now offering clinical trials as part of the ACTIV program potentially benefiting local residents. Given the paucity of deep research infrastructure in many regions across America, this largest county in New York by area, bounded by the St. Lawrence River and to the north Canada, stands out. And the health system offers two ACTIV research tracks, including ACTIV-1 and ACTIV-2 covering both those that have been infected by SARS-CoV-2 and who are admitted to the hospital (ambulatory care) and those that have been hospitalized. The principal investigator here reports on a good overall rewarding experience, especially when understanding the major academic centers involved with COVID-19 research and that a rural system, such as St. Lawrence Health System is right alongside world renowned centers.
As was recently reported in the Daily Yonder by Liz Carey, the NIH offers a wide spectrum of clinical trials covering the topic of COVID-19, from vaccines to advanced monoclonal antibodies, and for those COVID-19 patients in ambulatory care to those hospitalized.
The Region & COVID
A stunningly beautiful, forested and somewhat rugged rural area at the northern end of New York State, the county of St. Lawrence includes about 112,000 people living in an expanded 2,680 square feet making this region more dispersedly populated than most counties in the eastern United States. With a median household income of under $50,000, many up in these parts must make do with less financial resources. This county and surrounding counties are far away from any major city, 150 miles northeast from Syracuse and so far from New York or Buffalo that it’s hard to imagine this is the same state. Isolation is helped by geography as St. Lawrence County, situated north of the Tugg Hill plateau, which the Daily Yonder shares is “one of the snowiest places in the U.S.”
During the initial wave of the COVID-19 pandemic the region was hit hard with a high of new cases 10,794 in a day—nearly 10% of the population. Then the daily number of cases waned and the whole situation stabilized for much of the pandemic. Perhaps because of the rural, decentralized nature of the population distribution? From June to mid-September, the average number of cases per day totaled from a few hundred to several hundred but that was it. But the number of cases associated with the cold season showed up in force. By November, the cases were on the rise. By January 13, over 14,000 new cases were reported making the epidemic’s first wave look tame. Cases have been back on their way down to a reported 6,538 on Valentine’s Day. But there are a lot of people in this county and surrounding areas ill with COVID-19.
The distribution of COVID-19 deaths were greatest after the first wave in March and April with grisly days in this rural county with 1,003 fatalities alone on April 14. April was a horrific month here but then the deaths waned by late May and from then till December there were fatalities but they were in the single digits to dozens per day and no more. The death toll from this much larger second wave in the cold season is far less than the first one. Perhaps this reflects the medical professional community’s advancing knowledge as to how to treat the disease. And of course the Oxford RECOVERY trial breakthrough evidenced that dexamethasone can actually reduce the COVID-19 death rate under select conditions.
Principal Investigator Perspective
Dr. Eyal Kedar, a rheumatologist employed by the St. Lawrence Health System, serves as Principal Investigator for the ongoing studies here. Recently interviewed by Ms. Carey of the Daily Yonder, Dr. Kedar reports, “[The trials] a large number of the COVID-19 patients in our area with a potential treatment option that isn’t yet on the market.” He continued, “And since there’s so little clinical research infrastructure in general in rural America, we are the rare rural site that is able to offer these clinical trial options in the pandemic.”
Dr. Kedar reports that the health system uses both remdesivir (for hospitalized COVID-19 patients) which can reduce the duration of illness but not the death rate as well as dexamethasone which “can prevent death.”
The ACTIV-1 and ACTIV-2 studies are ongoing in this health system, reports Dr. Kedar. Both master protocols, ACTIV-1 centers on hospitalized adults with moderate to severe COVID-19 disease. The health system via the NIH tests a number of investigational therapies including infliximab (Remicade by Janssen/J&J), abatacept (Orencia, Bristol Myers Squibb) and cenicriviroc (CVC, AbbVie) according to the NIH website. With a focus on immune modulators to reduce the risk of the deadly cytokine storm, these three agents were selected due to their relevance based on initial review involving several factors including strong evidence for use against inflammatory reaction and cytokine storm, as well as general availability for large studies.
The ACTIV-2 master protocol, designed as a Phase 2 study can expand to Phase 3 seamlessly should the study drugs show efficacy. Tested in a population not hospitalized for COVID-19, the goal of this group of studies is to reduce the duration of symptoms and to test if the treatment can increase the proportion of participants with undetectable virus. The investigational therapies involved include Lilly’s LY-CoV555 (recently approved under emergency authorization known as Bamlanivimab as well as monoclonal antibodies from Brii Biosciences headquartered in China and Research Triangle in North Carolina. Also under investigation is a promising long-acting monoclonal antibody cocktail originally invented at Vanderbilt and licensed by AstraZeneca known as AZD7442 and finally an inhalable beta interferon investigational product from Synairgen. Inhalable and delivered via a nebulizer, the candidate is known as SNG001. Finally, the ACTIV-2 program also includes an orally administered serine protease inhibitor developed by Sagent Pharmaceuticals called Camostat mesilate. The NIH sought to test if this drug can block SARS-CoV-2 from entering the human cells.
The Health System
Established in 2013, St. Lawrence Health System was born to improve health and to expand access through coordination and integration of services. The health system serves as the largest employee in the county with 1,950 employees including 195 full-time licensed medical staff and estimated net operating revenue of $300 million.
This isn’t the first time this rural health system conducted clinical trials. Principal Investigator Dr. Kedar reports in the Daily Yonder that the health system has developed a clinical and rural health research department and has a number of studies under its belt. For example, its Research Department promotes clinical research involvement, education and compliance, delivering high-quality industry, investigator-initiated and rural health research programs.
Any decision to participate in clinical trials, now in the pandemic includes the COVID-19 treatment team, Department of Clinical and Rural Health Research and the administration of the St. Lawrence Health System.
Affiliation with Rochester Regional Health
Just in the New Year this health system became an affiliation of Rochester Regional Health (RRH), an internationally recognized integrated health services organization, earning accolades and awards from Healthgrades, America’s 50 Best Hospitals, multiple Magnet® Awards for nursing excellence and the greatest number of Beacon Awards for Excellence of any hospital system in the nation.
St. Lawrence Health System made the move to affiliate with RRH to offer patients more resources, innovative practices and technology, while mitigating rising costs. The goal of the two joining forces—introduce comprehensive, regionally integrated healthcare, bolstering population health management and advancing patient care. As part of this deal St. Lawrence merged onto the Epic Electronic Health Record by the end of year 1 of the affiliation.
A growing trend in rural regions, larger health systems and hospitals are using their major EHR implementation as a key selling point for merging activity. Smaller hospitals often struggle with these complex deployments. Moving forward the two announced that each patient in the St. Lawrence Health System will be connected to a single medical record and embedded clinical intelligence ensuring that clinical decisions are based on real-time, updated intelligence.
St. Lawrence Health System includes the following centers:
∙ Canton-Potsdam Hospital, a 94 bed, emergency medicine, acute care, critical care, Level III Trauma Center & 25 different specialties including cancer care
∙ Gouverneur Hospital (GH), not-for-profit critical access hospital launched in 2013, certified for 25 beds. Critical access is a federal designation assigned to rural hospitals enabling reimbursement options necessary for viability
∙ Massena Hospital, acute care, 25-bed hospital offering inpatient medical, surgical, labor and delivery, pediatric and emergency care.
Eyal Kedar, MD, Board Certified (American Board of Internal Medicine & Rheumatology)
Call to Action: Listen to Dr. Kedar on a podcast along with Carly Lovelett as they discuss how to build a better rural health-research system. This can lead to a reduction in health equity disparity while improving prospects for rural communities. Kedar manages his own website called Rural America and COVID-19.