When the World Health Organization recently named blood transfusions from Ebola survivors as its priority experimental therapy for the disease ravaging west Africa there was only one major problem: no data indicating that such transfusions work. Blood plasma from survivors contains antibodies that could potentially trigger an immune system response in patients, which would bolster their ability to fight the virus, but clinical data suggesting it has helped patients beat back the virus does not exist.
In the absence of any other approved therapy or vaccine for Ebola, however, a number of patients in the U.S. (including one of the first Americans to contract Ebola in this outbreak, aid worker Kent Brantly) have received blood transfusions from Ebola survivors. Such donated plasma needs to be screened for other blood-borne diseases such as HIV and hepatitis, which has complicated efforts to set up such protocols in the field. Now, the Bill & Melinda Gates Foundation has announced that in early 2015 it plans to begin clinical trials in Guinea to test if transfers of blood plasma are effective. The organization is putting up $5.7 million to support the work and is recruiting other donors for trials in Guinea and perhaps other Ebola-affected west African nations. Many details are not ironed out, including how many patients will be included. But the foundation’s grantee, David Hoover, senior medical adviser of Clinical Research Management, Inc., provided me with initial information by email.
[An edited version of the exchange follows]:
Q: Where will the trials be conducted?
A: The trials will be conducted in Guinea and other west-African countries that have been affected by the current Ebola epidemic. To date, we have only announced Guinea as a trial country. We will announce other countries once we have the agreement of national governments to do so.
Q: How will donors be recruited?
A: Donors will be recruited through organized groups of people who have survived Ebola and via survivor donor lists maintained by hospitals.
Q: Who will be qualified to donate convalescent (survivors’) plasma?
A: Ebola survivors who have been free of infection for at least 28 days will be qualified to donate. These survivors will visit a mobile laboratory that is equipped with plasmapheresis and pathogen inactivation devices.
Q: Will there be enough convalescent plasma to treat all interested patients?
A: We expect that demand for convalescent plasma will significantly exceed supply. For every two donors, the trial will be able to provide convalescent plasma to two recipients. [So each recipient will receive plasma collected from two donors rather than a single patient.] Trial participants who match the blood type of the donors will receive 600 milliliters of plasma administered in three, 200 milliliter doses over four days. Trial participants who don’t match the blood type of the donors will not receive convalescent plasma, but they will receive a higher standard of care for their Ebola infection than is generally available in Ebola-affected countries [since they will receive intravenous fluid replacement which is not available in many areas]. The trial has been designed to provide a completely objective selection of people receiving convalescent plasma.
Q: How did the researchers determine the dosage to be evaluated?
A: The dosage determination of three, 200 milliliter infusions of convalescent plasma per patient is based on anecdotal evidence from previous Ebola oubreaks. During the Kikwit outbreak in 1995, seven out of eight people who were treated with whole blood from recovered patients survived their infections. The trial is designed to deliver plasma doses that are equivalent to, or higher than, the doses that the Kikwit survivors received.
Q: What will the standard of care be for participants enrolled in the trial?
A: Everyone who is enrolled in the trial will receive infusions of intravenous fluids and electrolytes, as well as regular monitoring of vital signs, including electrolytes and blood pressure.
Q: How will researchers measure the effect of the convalescent plasma?
A: The effect of the plasma will be measured by tracking the level of virus in recipients’ blood versus the baseline control group [which has yet to be defined]. The trial will not be able to provide plasma to every patient who qualifies for trial enrollment, and plasma will be administered to the first available trial participants whose blood types match the available plasma.
Q: How will donors be compensated for their participation in the trial?
A: Donors will not be paid for the plasma that they have contributed. They will, however, receive subsidized travel and accommodation to facilitate their participation in the trial, and they will be compensated [financially] for their time.