Coronavirus: Scientists to trial drugs on Kiwi patients

Image: Getty
Image: Getty
Kiwi Covid-19 cases may soon be recruited for clinical studies looking at whether medicines used for malaria and HIV could help infected patients recover.

The studies – being hosted at Auckland City Hospital and others here and in Australia – are among a surge in trials investigating whether anti-viral drugs might offer a stop-gap defence against the new coronavirus until a vaccine could be found.

Covid-19-positive patients admitted to hospital - either in a medical ward, if their illness was not severe, or in an intensive care department, if their illness was severe – would be offered the option of taking part, said Associate Professor Mark Thomas, of the University of Auckland's School of Medical Sciences.

If patients or their family provide consent, they would be randomly allocated to treatment with hydroxychloroquine, an anti-malaria medicine, or with Kaletra, an anti-HIV medicine, or with a combination of both hydroxychloroquine and Kaletra, or with a placebo.

"Neither the patients, nor their family, nor the medical team caring for the patients, will know which of the four possible treatments the patients are receiving," Thomas said.

"It is what is called a double-blind study, which allows the effects, potentially beneficial, or harmful, to be evaluated without any bias affecting the evaluation of the effect of each treatment on patients' outcomes."

The trials, being overseen by the Australian and New Zealand Intensive Care Society, would help researchers understand whether the drugs were effective therapies for Covid-19.

"It is very likely that patients who are not participating in these studies will not be offered either or both of these medicines, because their medical teams will not know until this and other similar trials are completed, whether the medicines are helpful, or harmful, or have no discernible benefit or harm," he said.

"Other medicines are being evaluated in other studies overseas, but, in general these other medicines are not registered and available for use in New Zealand, and therefore not able to be used to treat patients in New Zealand."

A vaccine for Covid-19 was still likely to be 12 months away, despite a global scramble.

Kurt Krause.
Kurt Krause.
"Since both drug and vaccine development take such a long time, interest has arisen in already approved drugs that can be repurposed to target Covid-19," explained Professor Kurt Krause, of the University of Otago's Department of Biochemistry.

The repurposed drugs fell into three main groups: polymerase inhibitors, protease inhibitors and others.

"Polymerase inhibitors include some of the most promising options and the notable members of this group are remdesivir, galidesivir and favipiravir," Krause said.

"They work by blocking the enzyme that allows the virus to replicate its nucleic acid coding strand. If a virus cannot replicate its nucleic acid, it cannot replicate."

Remdesivir was approved for use in animals against diseases like FIP – or feline infectious peritonitis – and was being evaluated in a small clinical trial in China. Results are due next month.

"Favipiravir was developed in Japan and has shown early promising results, but nothing has been published in the peer reviewed literature yet," Krause said.

"Galidesivir is a polymerase inhibitor that was partly developed in New Zealand and has activity against coronavirus. It is being considered now for further studies and is notable for its strong New Zealand connection."

Protease inhibitors – which include Kaletra - were a major drug class in use against HIV, in which they worked by blocking an enzyme that processed proteins that the virus needed for growth.

Another repurposed drug being studied was camostat mesylate. Like Kaletra, it was a protease inhibitor, but acted in a different way.

"Camostat meslyate inhibits a completely different protease that is used by coronavirus to mediate its uptake into cells," Krause said.

"The good news that is that camostat is already used in people but for a non-infectious condition - chronic pancreatitis, but the cautionary note is that camostat has not yet been used in people for coronavirus treatment."

Chloroquine – typically used by travellers for protection against malaria - was among the other possibilities.

"It turns out that it happens to inhibit Sars2-CoV replication in the test tube and it has garnered wide attention because of it," Krause said.

"Physicians are keen to learn if this observation could be translated into success in living humans. A cautionary note is that chloroquine has been looked at before with other viruses and was not found to be effective."

There have been case reports from China and Italy of people in intensive care who have had various antiviral and antibiotic medications, but there was yet no clear indication that any of these helped, said Dr Christopher Gale, a senior lecturer at the University of Otago's Department of Psychological Medicine.

"What is happening is that various antiviral medications are being tested rapidly in the severe cases," Gale said.

"It will not take much time - or participants in the trials - to see if such a medication works or does not."

While some agents will be shown to work, others wouldn't be, and at that point the health system will be able to offer treatments for Covid-19 with confidence, he said.

"If and when we have treatments that work, then we will have to consider how we source them - which may include deliberately going off patent and getting pharmaceutical companies in New Zealand to make them."

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