COVID-19 | India to Begin Trial of Sepsis Drug; All That We Know

COVID-19 | India to Begin Trial of Sepsis Drug; All That We Know

In the search for ways of treating COVID-19 patients, one of the most sought-after approaches has been the ‘repurposing’ of drugs which have been found safe and efficient in their use against other diseases.

The latest name that has emerged for this purpose in India is Sepsivac, a drug used for treating patients suffering from gram-negative sepsis.

In the press briefing on 21 April, the representative of the health ministry said, “The Council of Scientific and Industrial Research (CSIR) will start a randomized clinical trial to evaluate the drug’s efficiency for reducing the mortality in critically ill COVID-19 patients. Considering the clinical similarity in gram-negative sepsis patients and COVID-19 patients, the Drug Controller General of India (DCGI) has approved the trial which will soon begin in multiple hospitals.”

Here’s what we know about the drug, the trial and the parallels drawn between the two infections.

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The Clinical Trial

The drug candidate ‘Sepsivac’ has been developed by Cadila Pharmaceuticals Ltd. in Ahmedabad with support from CSIR for the treatment of gram-negative sepsis (a kind of a severe blood infection) under the latter’s ‘New Millennium Indian Technology Leadership’ initiative.

The trial will be conducted at three hospitals, PGIMER, AIIMS Delhi and AIIMS Bhopal, and is expected to go on for up to six months, reports have stated. While AIIMS Bhopal has got its nod from the ethics committee, a response from the other two institutes is expected soon, Dr Shekhar Mande, Director General of CSIR said.

Dr Shekhar Mande“Extensive clinical trials have been conducted by Cadila Pharmaceuticals Ltd on preventing deaths against gram-negative sepsis, with more than 50% reduction in deaths of critically ill patients.”

“We are hoping that the clinical trials will show this to be equally useful in reducing deaths due to COVID-19,” he added.

On its website, Cadila Pharmaceuticals states that the drug contains ‘mycobacterium w’, which moderates the immune response in people with sepsis. It has been approved by DCGI for use in immunotherapy treatment in sepsis and sepsis shock. Randomized trials in these patients have shown 11 percent absolute reduction and 55.5 percent relative reduction in mortality. Sepsivac has also been found to reduce a patient’s days on ventilator, ICU stay, hospital stay and incidences of secondary infection.

All initial trials on sepsis patients were supervised by a CSIR-appointed monitoring team.

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Gram-Negative Sepsis & COVID-19: The Similarities

Researchers expect the drug to show promise in reducing the mortality among critically ill COVID-19 patients because the body’s response in severe cases of both infections is similar.

In conversation with FIT, Dr Prakash Doraiswamy, Senior Consultant, Critical Care and Anaesthesiology at Aster CMI Hospital, said, “The effects of sepsis and COVID-19 are similar in the sense that they are both pro-inflammatory and they both lead to clotting of blood vessels.”

Now how exactly does this work?

Dr Shahid Jameel, a well-known Virologist and CEO of Wellcome Trust DBT India Alliance, explained, “In sepsis, the body overreacts to an infection. In a normal immune response, certain molecules called cytokines are produced in the body. These signal the white blood cells to come to the site of infections and use their ability to destroy the viral or bacterial infection. Now, this is the body’s normal defense mechanism, where the production of cytokine is regulated.”

Dr Shahid Jameel“When the infection is overwhelming, the body increases its cytokine output and there is an overreaction of the immune system, which eventually starts attacking healthy tissues as well. This can lead to a condition known as ‘cytokine storm’, because of which many organs start shutting down. This multiple organ failure is one of the hallmarks of sepsis.”

In many people who are dying of COVID-19, a similar effect on multiple organs of the body is being observed, he adds. While the lung is deeply damaged, the virus and the body’s response to it could injure many other organs. “The infection seeps into all organs and has been seen to cause damage to the lungs, heart, kidneys, liver, blood vessels.”

Dr Shahid Jameel“A lot of this looks very much like sepsis, and that is the basis for trying out this drug. It is not expected to directly inhibit the virus, but it can help inhibit the body’s overreaction to the virus which leads to the infection.”

Dr Doraiswamy makes a similar point. “The trial is being conducted because the drug has been effective in blocking the molecule that causes inflammation in the body. The mediators of inflammation are similar in both infections, and so if the drug has worked in reducing the inflammatory response and thereby, mortality, in sepsis patients, the same may work for critically ill COVID-19 patients. That’s the basis of the experiment.”

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