Ketotifen as a Treatment for Vascular Leakage During Dengue Fever
Status:
Unknown status
Trial end date:
2017-07-01
Target enrollment:
Participant gender:
Summary
Rationale and Aims: Infection by dengue virus (DENV) causes major morbidity and mortality
throughout the world. In 2012, an estimated 3.6 billion people live in areas at risk for DENV
infection, including Singapore. The key pathology of DENV infection is vascular leakage,
which can occur in mild cases and can become life-threatening in severe cases when patients
may develop dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Mast cells (MCs)
are strongly activated by DENV with preliminary studies showing that activation levels are
correlated to disease severity in human patients. Thus, the investigators propose to use the
MC stabilizing drug, ketotifen, to limit the immune pathology that is characteristic of
dengue infection and treat dengue-induced vascular leakage. Methods: The ability of Ketotifen
to reduce vascular leakage in DENV patients will be determined by assessing the pooling of
fluid in the pleural cavity (measured by MRI and CXR) after 5 days of drug administration,
evaluated as a percent change compared to baseline fluid levels. Additional measures of
vascular leakage and immune pathology will be compared as secondary objectives. The trial
will be conducted as a randomized, double-blind study comparing the responses of dengue
patients given either ketotifen or placebo (n=55 per arm). Importance of proposed research:
Currently, no targeted treatments exist to limit vascular leakage during DENV infection. If
Ketotifen is identified as effective for preventing pleural effusion and/or plasma leakage in
DENV patients, this would constitute an advance for the clinical management of DENV fever.
This finding would also support a large-scale trial to determine whether Ketotifen can be
used to prevent severe vascular leakage as occurs during DHF/DSS. Benefits/Risks: Ketotifen
has a record of safety and tolerability in humans, regulatory approval, and widespread use.
Side effects are generally mild. The potential exists that, if effective, many of the painful
and life-threatening symptoms of DENV infection that result from plasma leakage would be
improved.
Phase:
Phase 4
Details
Lead Sponsor:
National University Hospital, Singapore
Collaborators:
Duke-NUS Graduate Medical School Singapore General Hospital