publication date: May. 29, 2020
Study: Hydroxychloroquine doesn’t improve survival in hospitalized COVID-19 patients, but tocilizumab does
An observational study of more than 3,000 patients hospitalized with COVID-19 at Hackensack Meridian Health has shown that hydroxychloroquine doesn’t improve survival for hospitalized patients.
However, tocilizumab appears to improve survival among critically ill intensive care unit patients, the study showed. If confirmed, tocilizumab would become the first medication improving survival from COVID-19.
Hackensack Meridian Health released the findings on medRxiv, which allow researchers to share critical scientific information rapidly prior to publication in peer-reviewed journals.
The results are based on the new data analysis platform—the HMH Universal Observational Database for COVID-19, or RECOVERY, which compiles outcomes from 13 Hackensack Meridian Health hospitals throughout New Jersey.
“Our researchers’ observations that tocilizumab may improve survival among the most critically ill could alter the course of the pandemic if confirmed in randomized trials—and Hackensack Meridian Health is participating in those randomized trials as well,” Robert C. Garrett, chief executive officer of Hackensack Meridian Health, said in a statement.
The outcomes division of the John Theurer Cancer Center at Hackensack University Medical Center, under the leadership of Stuart Goldberg and Andrew Ip, created a database to guide the analysis of more than 3,000 patients admitted to Hackensack Meridian Health facilities for urgent care.
Results from the study follow:
Among 2,512 hospitalized patients with COVID-19, 76% received at least one dose of hydroxychloroquine and 59% received hydroxychloroquine with azithromycin.
After adjusting for imbalances via propensity modeling, compared to receiving no hydroxychloroquine, there was no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospital stay.
Among 547 ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival rate: 56% who received the drug compared to 46% who did not receive the therapy, and a propensity adjusted hazard ratio 0.76.
The Hackensack Meridian JTCC team worked with COTA Inc., to conduct propensity modeling to assess for potential effective therapeutic interventions. The data and statistical analysis were enhanced by Donald A. Berry, professor in the Department of Biostatistics at MD Anderson Cancer Center, and his statistical team at Berry Consultants.
“Our study adds to the emerging data finding no benefit for hydroxychloroquine among hospitalized patients, but now we will turn our database’s attention to exploring if the medication is beneficial earlier in the pre-hospital course,’’Andre Goy, physician in chief at Hackensack Meridian Health Oncology and chairman and chief physician officer at John Theurer Cancer Center, said in a statement.
Researchers established an observational database through Epic–Hackensack Meridian’s electronic health records system—and collected a random sampling of COVID-19 patients who received treatment at one of 13 hospitals across the network. To date, Hackensack Meridian Health has cared for more than 10,000 patients with confirmed COVID-19 infections and has discharged more than 6,000 patients from network hospitals.
Genentech begins phase III trial of tocilizumab + remdesivir in hospitalized patients with severe COVID-19 pneumonia
Genentech, a member of the Roche Group, has launched a phase III, randomized, double-blind, multicenter study (REMDACTA) to evaluate the safety and efficacy of Actemra (tocilizumab) plus the investigational antiviral remdesivir, versus placebo plus remdesivir in hospitalized patients with severe COVID-19 pneumonia.
The trial, in collaboration with Gilead Sciences Inc., is expected to begin enrolling in June with a target of 450 patients.
“Based on our current understanding, we believe that combining an antiviral with an immune modulator could potentially be an effective approach to treating patients with severe disease,” Levi Garraway, Genentech chief medical officer and head of global product development, said in a statement.
In addition to REMDACTA, Genentech is close to completing enrollment of the global randomized, double-blind, placebo-controlled phase III clinical trial (COVACTA, NCT04320615) to evaluate the safety and efficacy of intravenous Actemra plus standard of care, versus placebo plus SOC in hospitalized adult patients with severe COVID-19 pneumonia.
Approximately 450 patients will be enrolled in COVACTA. This is an increase from the original target of 330 patients. Actemra is not currently approved for this use by FDA.
The protocol for COVACTA allows the inclusion of patients who are being treated with antivirals, including investigational antivirals. Data from the REMDACTA trial are designed to supplement the COVACTA study.
The COVACTA study is conducted in collaboration with FDA and the Biomedical Advanced Research and Development Authority. Genentech is also a participant in the Accelerated COVID-19 Therapeutic Interventions and Vaccines partnership, led by NIH and the Foundation of the NIH.
Genentech has also initiated a national phase III double-blind, placebo-controlled randomized trial (EMPACTA, NCT04372186) that will focus on recruiting approximately 375 patients at trial sites known to provide critical care to underserved and minority populations that often do not have access to clinical trials.
UMich develops app that calculates risk of delaying cancer care during COVID-19
A team of data scientists and cancer doctors from the University of Michigan Rogel Cancer Center and the U-M School of Public Health developed a free, web-based application to compare the long-term risk for a patient whose cancer treatment was postponed.
The OncCOVID app draws on national cancer data sets to help assess the risk of immediate treatment versus delayed treatment, depending on a patient’s individual characteristics, as well as on COVID’s impact on their local community.
“We also see the app providing additional reassurance to oncologists and their patients when the data show that delaying treatment will likely have little or no impact on a patient’s long-term outcome,” the project’s lead researcher, Holly Hartman, a doctoral student in biostatistics at U-M, said in a statement.
OncCOVID could also be used by health care systems resuming care and need to prioritize a backlog of patients.
“Hospitals have basically been using a three-tiered system during COVID: treat, delay a little, or delay a lot,” Daniel Spratt, associate professor of radiation oncology at Michigan Medicine and one of the senior researchers on the project, said in a statement. “Unfortunately, this tiered system is an extremely blunt instrument. Our goal was to create a resource that could be tailored both to the individual patient and to their local community.”
The app allows doctors to enter more than 45 characteristics about a patient — including their age, location, cancer type and stage, treatment plan, underlying medical conditions, and the proposed length of a delay in care. It then calculates the patient’s likely five-year survival following immediate treatment and delayed treatment.
Under the hood, the app draws on millions of records contained in the National Cancer Institute’s Surveillance, Epidemiology, and End Results registry and the National Cancer Database, combined with county-level COVID infection data from Johns Hopkins University.
Advanced features allow all of the app’s underlying statistical assumptions to be adjusted, such as the baseline mortality risk from COVID and the disease’s infection rate. In the future, the researchers plan to use the same data model to start looking at the effects that treatment delays due to the coronavirus pandemic may have on cancer mortality nationally, Hartman said.
ACS CAN survey: cancer patients increasingly face COVID-19 health impact
In a survey conducted by the American Cancer Society Cancer Action Network survey of cancer patients and survivors, 87% of respondents said the COVID-19 pandemic had affected their health care in some manner, up from 51% in an April survey.
Of those in active treatment 79% reported delays to health care (up from 27%), including 17% of patients who reported delays to their cancer therapy like chemotherapy, radiation or hormone therapy. The most commonly reported effects for those in active treatment were for changes to in-person cancer provider appointments (57%*); and delays in access to imaging services (25% up from 20%) and surgical procedures (15% up from 8%). Delayed access to supportive services, including physical therapy or mental health care, remained steady (20%).
Nearly one in four patients surveyed say the pandemic has made it more difficult to contact their providers with questions about their health care needs, and one in five say they are worried their cancer could be growing or returning due to delays and interruptions caused by the COVID-19 outbreak.
Forty-six percent said the COVID-19 pandemic had impacted their financial situation and ability to pay for care in some way (up from 38%). And nearly a quarter (23%) said they worry they may lose their health insurance due to the pandemic and its effects on the economy.
While a majority of respondents said they are sheltering in place, 18% said they were working outside the home, including 11% of those still in active treatment. More than a third (34%) of patients say they are anxious the pandemic will make it hard to afford basic household expenses; concerns that are especially prevalent among lower-income patients with more than half (54%) of those earning $30,000 or less reporting that they are worried about affording essentials, including rent, food and utilities.
This combined medical and financial stress has resulted in nearly half (48%) of patients saying the COVID-19 pandemic has had a moderate or major effect on their mental health. In particular, 67% said they worry it will be harder for them to stay safe when social distancing and other restrictions are relaxed in their area, and 70% of patients worry they will be unable to find protective equipment like gloves or masks to help keep them safe.
The survey also collected feedback from a small group of providers and caregivers who similarly reported concern about delayed care and difficulties providing support for patients while being unable to see them, as well as a lack of personal protective equipment. Caregivers, like patients, reported anxiety over reopening and the increased potential for their and their loved one’s exposure to the virus.
The web-based survey was taken by more than 1,200 cancer patients and survivors. This sample provides a margin of error +/- 3% and 96% confidence level. Additional input was provided by 111 caregivers and 139 health care providers supporting cancer patients and survivors.