Controlled Trials of Plasma Therapy Begins India

Controlled Trials of Plasma Therapy Begins India

ICMR has given node for Convalescent Plasma Therapy Clinical Trials, the treatment’s efficacy still needs to be tested. Since convalescent plasma therapy is an experimental procedure, the Indian Council of Medical Research recommends that the therapy be only used as a part of clinical trials.

What Is Convalescent Plasma Therapy?

  • Plasma is the component of the blood that contains the virus-fighting antibodies.
  • For convalescent therapy, plasma is extracted from the blood of recovered COVID-19 patients and given to people severely ill with the disease.
  • It helps severely ill patients fight the infection by reinforcing their immune system.

Why Blood Plasma?

  • It is safe.
  • Plasma transfusion from recovered Covid-19 patients lowered the severity of the disease by lymphocyte counts, improving liver and lung functions, and reducing inflammation, which is a sign of infection, reported a study earlier this month in the proceedings of the
  • National Academy of Science.
  • Convalescent therapy was used with success during the 1918 Spanish Flue Pandemic.
  • The World Health Organisation recommended its use against Ebola and issued a protocol for its use to treat Middle East Respiratory Syndrome.

HOW Does IT Work?

  • When the virus enters the human body, the immune system creates an antibody to fight it. This antibody remains in a person even after the virus has cleared out of their system. In the absence of other drugs, experts say that using these antibodies from recovered patients can offer a reprieve to severely ill Covid-19 patients.
  • The therapy involves drawing out whole blood from a patient who has recovered from Covid-19 at least two weeks after testing negative for the disease. The plasma is separated and 400 ml of plasma can be used to treat two patients. The therapy uses the antibodies generated from the recovered patient to treat others suffering from the illness.

Source of Blood Plasma:

  • “Now, there are over 1,600 people who have recovered from Covid-19 in the country and their blood plasma can be used to treat those who are critical. The antibodies from the recovered person will theoretically help the critical patients in fighting the infection. This is done for other viral illnesses as well,” said Dr. SK Sarin, director of the Institute of Liver and Biliary Sciences:
  • As for donors, only health individuals – with no comorbidities like diabetes, hypertension, or heart disease and less than 60 years of age – who have recovered from the infection would be selected.

Eligibility of Patients:

  • Hospitalised and critically ill coronavirus-hit patients fulfil the inclusion criteria. Also, those admitted or cared at COVID-19 management facilities in India will be eligible for inclusion in the trial.
  • The plasma is transfused into the body of an admitted patient and it may prevent clinical infection or it may reduce the severity of the infection among those who have recently been exposed
  • The therapy would be given only to patients in a critical condition — those with a respiratory rate higher than 30 breaths per minute (the normal is 18-20 breaths per minute), have an oxygen saturation of less than 90% (normal is 95 to 100%), or have infiltrated like pus in the lungs.

Evidence of Success of the Therapy:

“There are anecdotal evidence to say that Covid-19 patients on plasma therapy have recovered in other countries. However, we need to ensure that the therapy is given to people who are at high risk before they are on a ventilator. This is because the antibodies can prevent the progression of the disease by reducing the viral load, it cannot heal the lungs and the other organs. So, if a person already has lung damage and is in multi-organ failure then the therapy will not be useful,” said Dr Shobha Broor, former head of the department of microbiology at the All India Institute of Medical Sciences.

In a randomised control trial, which is suggested by the ICMR, half the patients receive the plasma and the other half receive a placebo. This helps the doctors in determining whether people on therapy do better than those not on it.

Though there is an element of uncertainty over how good the antibodies are, epidemiology experts said this can be addressed with antibody testing kits. India received about half a million antibody test kits on Thursday.

Benchmark for Hospitals Who Can Use the Convalescent Plasma Therapy:

  • Develop a trial protocol that has to be approved by the Institute Ethics Committee.
  • Hospitals then must register with the Clinical Trial Registry of India.
  • They also must register with the country’s apex drug regulator, Central Drug Standard Control organisation (CDSCO).
  • Hospitals must also put in place the protocols to report serious adverse events to CDSCO.

Invitation to Capable Institutions Who Can Participate In Clinical Trials:

The Indian Council of Medical Research (ICMR) has invited capable institutions to participate in clinical trials to study the safety and efficacy of convalescent plasma therapy and therapeutic plasma exchange in limiting complications in COVID-19 patients.

The top biomedical research body has also made it clear that at this moment, it does not recommend this as a treatment option outside of clinical trials.

In a call to institutions that were made public, ICMR said institutions that have the required equipment and infrastructure can submit a letter of intent and they can participate in controlled clinical trials subject to approvals of the Drug Controller General of India (DCGI) and Institutional Ethics Committee.

Six institutes have applied for trials.
In Delhi, following two institutes have applied for the trials

  • Institute of Lever and Billary Science, New Delhi
  • Max Hospital Saket, New Delhi

Machines/Equipments Required For Starting The Treatment:

  • For the treatment, a plasmapheresis machine is used to derive plasma from the blood, which is then administered to patients with severe infection. Blood donated by patient recovered from Covid-19 is processed in the machine for being used for plasma therapy in a designated hospital.
  • This method is, however, not new and is used for the treatment of several other diseases.

A device being used for plasma therapy to treat other patients with coronavirus. (Reuters file photo).

Source of Blood Plasma:

As part of the convalescent plasma therapy, plasma is collected from a donor who has fully recovered from COVID-19 infection and has spent 14 days in quarantine after discharge. The plasma contains antibodies that can neutralise the virulence.
Depending on the bodyweight of a donor, between 600 to 800ML of plasma can be donated. The plasma has to be transported in a cold chain and it can also be stored for future use.

“Now, there are over 1,600 people who have recovered from Covid-19 in the country and their blood plasma can be used to treat those who are critical. The antibodies from the recovered person will theoretically help critical patients in fighting the infection. This is done for other viral illnesses as well,” said Dr SK Sarin, director of the Institute of Liver and Biliary Sciences:
As for donors, only health individuals – with no comorbidities like diabetes, hypertension, or heart disease and less than 60 years of age – who have recovered from the infection would be selected.

Evidence of Success of the Therapy:

“There are anecdotal evidence to say that Covid-19 patients on plasma therapy have recovered in other countries. However, we need to ensure that the therapy is given to people who are at high risk before they are on a ventilator. This is because the antibodies can prevent the progression of the disease by reducing the viral load, it cannot heal the lungs and the other organs. So, if a person already has lung damage and is in multi-organ failure then the therapy will not be useful,” said Dr Shobha Broor, former head of the department of microbiology at the All India Institute of Medical Sciences.
In a randomised control trial, which is suggested by the ICMR, half the patients receive the plasma and the other half receive a placebo. This helps the doctors in determining whether people on therapy do better than those not on it.

Expert’s Opinion:

Experts feel that not giving the treatment to half the patients under randomised control trial is unethical. Dr. T Jacob John, professor emeritus and former head of the department of virology at Christian Medical College, Vellore, said “Plasma therapy is already being used for three categories of ailments:

  1. Viral infection such as hepatitis or even chicken pox that can be severe in immunocompromised patients.
  2. it is done for autoimmune disorders, and
  3. Conditions like hemophilia in which the people receive proteins other than antibodies – like factor 8 in this case – through plasma therapy,”

“When it is an already established procedure, why should it not be administered to all the patients who are very sick? Not giving it to half the patients in need is actually an ethical problem, I feel,” said Dr. T Jacob John.

According to a scientific paper published in The Journal of Clinical Investigation, passive antibody therapy is most effective when it is administered prophylactically or used early after the onset of symptoms.

A recently published report on a trial in China showed an improvement in the clinical conditions of 10 people who received the therapy. “All symptoms in the 10 patients, especially fever, cough, shortness of breath, and chest pain, disappeared or largely improved within 1 day to 3 day upon Convalescent plasma transfusion,” the study published in PNAS Journal said.