The CLEAR-IVH trial, completed in 2008, was a phase-II feasibility and dose-finding trial conducted at 20 centers in the U.S., Canada, U.K. and Germany. There were 3 phases: Safety, CLEAR A and CLEAR B. The study enrolled 52 patients having a confirmed diagnosis of intraventricular hemorrhage (IVH) with third or fourth ventricle obstruction. Patients were given a thrombolytic, recombinant tissue plasminogen activator (tPA), via a extraventricular catheter (EVD) in one of three dosing regimens over a 3 day period. Results of the study were presented by Dr. Daniel Hanley of Johns Hopkins University, lead investigator, at the 2008 European Stroke Conference in Nice, France.
This study provided an early demonstration that treatment of IVH with catheter-delivered low-dose tPA can be safe and holds significant promise for becoming a safe, life-saving treatment for this devastating and usually lethal form of hemorrhagic stroke. In this relatively small group of IVH patients, 40% recovered to the point of living independently and 10% were completely normal with no deficits at the end of the 6-month follow-up period. The 30-day mortality rate was 15% compared to a typical rate of 80-85%.
The Intraventricular Hemorrhage Thrombolysis Trial was supported by grants (FD-R-001693 to Dr. Naff and Dr. Hanley) and (FD-R 002018 to Dr. Hanley and Dr. Rhoney) from the Office of Orphan Products Development, Food and Drug Administration. Dr. Naff received funding from the American Heart Association and funding from a research grant (FD-R-001693) from the Office of Orphan Products Development. Dr. Penelope Keyl received funding from a research grant (FD-R-001693) from the Office of Orphan Products Development. Karen Lane and Nichol McBee received funding from a research grant (FD-R-001693) from the Office of Orphan Products Development. Dr. Stanley Tuhrim received funding from a research grant (FD-R- 001693) from the Office of Orphan Products Development. Dr. Anthony Marmarou received funding from a research grant (FD-R-001693) from the Office of Orphan Products Development. Dr. Daniel Hanley is supported by grants U01NS062851 and RO1NS046309 from the National Institutes of Health/NINDS, grant 272-2007 from the Eleanor Naylor Dana Charitable Trust, the Jeffrey and Harriet Legum Endowment and materials grants from Genentech, Inc.
The study results established the optimal dosage, validated the dosing procedure and provided justification for launching the large phase-III trial, CLEAR-III in mid-2009.
Published in Stroke. 2011;42:3009-3016