The next stage of the THINKER project — THINKER-NEXT — is aiming to settle any lingering concerns that patients and centers might have about using kidneys from hepatitis C (HCV)-infected donors and transplanting them into HCV-negative recipients in need of a kidney transplant.

Armed with an $8 million grant from the National Institutes of Health, researchers at the University of Pennsylvania in Philadelphia will evaluate the long-term risks and benefits of transplanting kidneys from HCV-positive donors into HCV-negative recipients and compare outcomes with those attained following transplantation of HCV-negative kidneys into HCV-negative recipients.

“Most of the studies that have been done so far, including the MYTHIC study, were pretty small — MYTHIC had only 30 patients — so what’s quantitatively different about THINKER-NEXT is that it will involve 200 kidney transplants at eight centers and, as it is a registered trial, there will be a very careful assessment of any adverse reactions,” Peter Reese, MD, professor of medicine and epidemiology, Perelman School of Medicine, Philadelphia, Pennsylvania, told Medscape Medical News.

“So I think the study will give us more definitive data, and hopefully these data will prove to be more reassuring to patients and centers nationwide,” he added.

The trial will take place over the next 5 years and will be led by Reese and Douglas Schaubel, PhD, professor of biostatistics, University of Pennsylvania.

THINKER Trial

In the first stage of the project, lead investigators Reese and David Goldberg, MD, now at the University of Miami in Florida, learned they could cure HCV in transplant recipients using a full regimen of grazoprevir in combination with elbasvir, with or without ribavirin (Zepatier, Merck).

“So far, the cure rates have been 100% in studies where patients were given a full course of antiviral treatment,” Reese said. “That is what we are hoping to find in our study and that is what we expect.”

Now, however, Reese and his fellow investigators also want to understand: How well do HCV-infected organs function when compared to others? Do patients who receive these organs experience any unique complications? Are they susceptible to any other viruses such as cytomegalovirus?

Answers to these and related questions are urgently needed as hundreds of kidneys from HCV-positive donors are still being discarded each year despite a waitlist of between 90,000 to 100,000 patients awaiting a donor kidney each year in the United States. “We know right now that many centers do not accept any of these [HCV-positive] kidneys — probably still half of them,” Reese said.

Decreasing Discard Rate, Increased Competition

This is still much better than when PENN-State researchers started using HCV-positive kidneys about 5 years ago when most were thrown away, he added. “The discard rate has gone down,” Reese affirmed, increasing the number of patients receiving a donor kidney by between 500 and 1000 extra kidney transplants a year. “We’re super happy about that, these kidneys have definitely expanded the transplant pool,” Reese said.

The flipside is that there is more competition for HCV-positive organs now. “When we started, a patient could sign up for these organs and get a transplant very quickly,” Reese recalled. “That’s no longer the case as enough centers have recognized that these kidneys are valuable, so now, patients may shorten their waiting time only by a bit if they sign up for these organs,” he observed.

Should THINKER-NEXT succeed in convincing the medical community that HCV-infected donor kidneys are safe to transplant, often skeptical patients may still need convincing. “I’ve probably talked to about 100 patients about these organs and people just weigh risks very differently,” Reese acknowledged.

“For some patients, they get nervous when they hear the word ‘virus’; for others, they have concerns about the stigma associated with HCV as these kidneys often come from drug users, so there are definitely a number of patients who will still say, ‘No thanks, I’m looking for a more straightforward experience,” he added.

“So information [from THINKER-NEXT] will be very important if we are to increase adoption of this practice across the country,” Reese emphasized in a statement.

The study was funded by the National Institutes of Health. Gilead Sciences is donating study drug sofosbuvir/velpatasvir (Epclusa). Reese has reported no relevant financial relationships.

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