Varicella Zoster Infection Clinical Trial
Official title:
Efficacy and Safety of a Novel Intradermal Live-attenuated Varicella Zoster Vaccine in Hematopoietic Stem Cell Transplantation Donors: a Randomized Double Blind Placebo-controlled Trial
Hematopoietic stem cell transplantation (HSCT) is well-established therapy for patients with malignant hematological diseases. Varicella zoster virus (VZV) reactivation, clinically manifested as herpes zoster (HZ), is a major complication that affects up to 50% of patients. Most patients will require hospitalization. Despite treatment with high dose acyclovir, patients may develop severe complications including the disabling postherpetic neuralgia, corneal ulceration, viral dissemination and secondary bacterial infection. The median onset of infection is the fifth month following transplantation, with 91% of cases occurring within the first year. Direct vaccination of transplants recipients with subcutaneous live-attenuated VZVv before transplantation and up to one year after transplantation is contraindicated. A small prospective non-randomized study has demonstrated that subcutaneous vaccination for donors before HSCT may offer some protection against VZV reactivation in the recipients. Recently, dose-sparing influenza vaccine delivered via a novel intradermal microneedle has been shown to elicit a good immunogenic response in both healthy and elderly subjects. We sought to assess the efficacy and safety of the novel intradermal live-attenuated VZVv in sibling donors undergoing HSCT.
Hematopoietic stem cell transplantation (HSCT) is well-established therapy for patients with
malignant hematological diseases. Varicella zoster virus (VZV) reactivation, clinically
manifested as herpes zoster (HZ), is a major complication that affects up to 50% of patients.
Most patients will require hospitalization. Despite treatment with high dose acyclovir,
patients may develop severe complications including the disabling postherpetic neuralgia,
corneal ulceration, viral dissemination and secondary bacterial infection. The median onset
of infection is the fifth month following transplantation, with 91% of cases occurring within
the first year. Direct vaccination of transplants recipients with subcutaneous
live-attenuated VZVv before transplantation and up to one year after transplantation is
contraindicated. A small prospective non-randomized study has demonstrated that subcutaneous
vaccination for donors before HSCT may offer some protection against VZV reactivation in the
recipients. Recently, dose-sparing influenza vaccine delivered via a novel intradermal
microneedle has been shown to elicit a good immunogenic response in both healthy and elderly
subjects. We sought to assess the efficacy and safety of the novel intradermal
live-attenuated VZVv in sibling donors undergoing HSCT.
We plan to enroll 160 pairs of adult donors and patients who undergo allogeneic HLA matched
sibling HSCT in this prospective randomized double-blind placebo-controlled trial over a
period of 3 years. Enrolled donors and patients will be randomized into 4 groups: Group 1:
intradermal full dose live-attenuated VZVv; Group 2: subcutaneous full dose live-attenuated
VZVv; Group 3: intradermal 0.9% normal saline as control; Group 4: subcutaneous 0.9% normal
saline as the second control
All vaccines will be given to the donors within 28 days before HSCT. All intradermal vaccines
will be given via a microneedle syringe. Both the investigators and participants will be
blinded to the randomization process. The primary end point is the occurrence of HZ in the
patients within 12 months of transplantation. The secondary end points are the safety and
immunological response in the patients and donors.
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