COVID-19: Digestive symptoms of the novel virus and implications for clinical trials

As the entire healthcare ecosystem grapples with the COVID-19 virus, more evidence surfaces every day of manifestations beyond fever, respiratory symptoms and fatigue. In fact, a recent publication in the American Journal of Gastroenterology¹ concluded that digestive symptoms, such as abdominal pain, nausea, vomiting, diarrhea and loss of appetite, are common in patients with COVID-19.

Because of the lack of respiratory symptoms, these patients typically wait longer from onset of illness to seek care and be admitted to the hospital. The index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. This knowledge may help with earlier identification of COVID-19, faster time to treatment, earlier quarantine and lower exposure to bystanders.

Implications for Clinical Trials

The global pandemic has significantly impacted trial enrollment. With uncertainty over how long the pandemic will last, many large studies are temporarily on hold; project cancellations are widespread, and more than two-thirds of sites have closed to enrollment.

Given that COVID-19 infection can present with gastrointestinal and liver abnormalities without respiratory illness in asymptomatic volunteers in Phase I trials, ongoing clinical trials may incorrectly report these symptoms as serious adverse events (SAEs). Likewise, ongoing trials might incorrectly attribute these findings, such as elevated liver enzymes, to the investigational drug.

Special considerations must be given to patients with inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), who are currently in clinical trials. Experts from the American Gastroenterological Association (AGA) and The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) have made a number of valuable recommendations.²

In patients with underlying chronic liver diseases who are in clinical trials, the recommendations are less clear. It is not known if patients with chronic viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD/NASH), decompensated cirrhosis and other genetic/metabolic liver conditions are at higher risk of COVID-19 infection. Patients on immune-suppressing medications for hepatocellular carcinoma and to prevent rejection of a liver transplant should be considered at increased risk for COVID-19, although it is not clear if they are at risk for more severe infection. It has been suggested that immunosuppression prolongs viral shedding. It is uncertain if COVID-19 exacerbates these underlying liver conditions. However, experts from the American Association for the Study of Liver Diseases (AASLD) have issued preliminary guidance.³

Parexel is in a unique space to support the development of diagnostics and therapeutics for this pandemic. As of May 2020, Parexel is involved in more than 150 studies related to COVID-19, including:

• Clinical trials with directly acting anti-viral drugs, which can potentially “cure” the disease
• Immunomodulatory therapies to dampen the cytokine storm, which occurs as a reaction to the virus and increases morbidity and mortality
• Vaccine development for several unique COVID-19 targets with several different pharmaceutical companies
• Diagnostic devices to rapidly assess for the presence of the infection

Parexel is embracing a full range of virtual solutions that can be incorporated into clinical trials, whenever possible, to help minimize disruptions due to COVID-19. These approaches include:

• Decentralized Clinical Trials (DCTs): Developed within our Patient Innovation Center, these are available as both fully virtual and hybrid options. With more than 70 DCTs underway or completed, and experience in more than 200 remote patient-engagement strategies, Parexel is a leader in this industry. Bringing trials to the patient’s home or local community allows those from diverse populations and geographies to gain access to ground-breaking research.
• Direct-to-Patient Offering: Parexel is the only CRO with its own global distribution center, allowing expedited shipment of equipment and supplies directly to the patient.
• Data-driven monitoring and remote monitoring with telemedicine visits: As both a software company and a full-service CRO, Parexel is one of the leaders in the field offering technology and integration solutions to successfully complete DCTs.

References

1. Pan L et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. American Journal of Gastroenterology 2020;March 18: [Epub ahead of print].
2. Rubin DT, Abreu MT, Rai V, Siegel CA, on behalf of the International Organization for the Study of Inflammatory Bowel Disease, Management of Patients with Crohn’s Disease and Ulcerative Colitis During the COVID-19 Pandemic: Results of an International Meeting, Gastroenterology (2020), doi: https://doi.org/10.1053/j.gastro.2020.04.002.
3. Fix OK et al. Clinical Best Practice Advice for Hepatology and Liver Transplant Providers During the COVID-19 Pandemic: AASLD Expert Panel Consensus Statement. Hepatology 2020;April 16: [Epub ahead of print]. https://doi.org/10.1002/hep.31281.

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