Research examines novel treatment techniques for hemophilia B, VTE

May 26, 2017

A presentation during the 2010 ASH Meeting revealed preliminary results of the study, which evaluated two dose levels of a viral vector that enabled the transfer of a normal gene for FIX sufficient to generate therapeutic levels of the protein without causing adverse effects in four patients. Since then, investigators have administered the vector in two additional patients with severe hemophilia B at a higher dose and have now followed the entire cohort six to 16 months post treatment.

The six trial participants were given an infusion that contained a vector carrying a normal copy of the FIX gene via a vein in the arm. Two subjects were treated with a low dose, two with an intermediate dose, and two with a high dose of the vector. Vector-mediated levels of FIX rose from less than 1 percent of normal before therapy to between 2 percent and 12 percent of normal levels in all six patients. The FIX levels, in the first subject who has been followed for the longest time, have remained at 2 percent for more than 12 months following gene transfer. The highest level of FIX expression has been observed in the two subjects treated at the highest dose level, with expression ranging from 3 percent to 12 percent. Four of the six participants have discontinued prophylactic treatment and remain free of spontaneous bleeding, and the remaining two patients have increased the time interval between FIX infusions.

"We have developed a vector for gene transfer that is more efficient and effective than traditional treatment for patients with severe hemophilia B by preventing spontaneous bleeding in this high-risk patient population," said Dr. Nathwani. "Our novel approach shows promise for improved gene therapy of hemophilia B and other protein deficiencies."

Dr. Nathwani will present this study during the Plenary Scientific Session on Sunday, December 11, at 3:25 p.m. PST at the San Diego Convention Center in Hall AB.

Improved Functional Outcome After Additional Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis: Results of a Randomized Controlled Clinical Trial (The CaVenT Study) [LBA-1]

In the largest randomized study performed to date, researchers have found that additional treatment with catheter-directed thrombolysis (CDT), when compared to standard treatment of oral anticoagulation therapy and elastic compression stockings (ECS), reduces the risk of post-thrombotic syndrome (PTS) in patients who suffer from deep-vein thrombosis (DVT) in their lower limbs.

PTS, a chronic complication of DVT that causes swelling, pain, cramping, and venous ulcers, occurs in approximately one in four patients who suffer from lower-limb DVT treated with standard therapy.

To reduce the risk of developing PTS, additional therapy is needed via catheter-directed thrombolysis (CDT), a minimally invasive procedure that uses x-ray imaging to administer medication to help dissolve clots through a catheter placed in the vein. CDT has become standard of care for the prevention of PTS in some treatment centers, despite a lack of randomized, controlled trials demonstrating its efficacy and safety, as well as several drawbacks including its high expense, association with life-threatening bleeding, and tendency to convert DVT (typically an outpatient condition) to an in-patient disease requiring hospitalization.

To evaluate whether additional treatment of DVT with CDT with alteplase (a clot-dissolving medication) reduces PTS development following acute iliofemoral DVT (occurring in the upper thigh and/or pelvic area), researchers embarked on the Catheter-Directed Venous Thrombolysis in Acute Iliofemoral Vein Thrombosis (CaVenT) study, a large, four-year, multicenter, randomized controlled trial.

In this trial, 209 patients between the ages of 18 and 75 with a first-time acute iliofemoral DVT, with symptoms present for up to 21 days, were randomized into two treatment arms: Treatment arm A (the CDT-treated arm) had 101 patients and arm B (control arm treated with oral anticoagulant and ECS) had 108 patients. The primary endpoint of the trial was the frequency of PTS after 24 months of follow-up.

Of the 90 CDT-treated patients and 99 control patients who had data available for analysis, 41.1 percent of patients treated with CDT presented symptoms of PTS compared to 55.6 percent of control patients. The difference in PTS incidence corresponds to an absolute risk reduction of 14.4 percent in patients treated with CDT.

Twenty bleeding complications were reported, three classified as major and five considered clinically relevant. None of the reported bleeding episodes caused serious complications, and there were no pulmonary emboli, strokes, or deaths related to treatment with CDT. After six months of follow-up, PTS developed in 36.9 percent of patients who no longer had a clotted vein, as compared to 61.3 percent of patients who still experienced clotting. These outcomes underscore the importance of recanalization, the unblocking of a blood vessel, for preventing PTS and ensuring positive outcomes in patients with DVT.

"The results of our trial show that additional treatment with CDT significantly reduces the risk of PTS in patients with DVT, compared to standard treatment alone," said Per Morten Sandset, MD, PhD, senior author and Head of Research, Clinic of Cancer, Surgery, and Transplantation at Oslo University Hospital in Norway. "Although CDT is a promising treatment option for patients with iliofemoral DVT, the therapy also increases the risk of bleeding, emphasizing the importance of patient selection and safety when performing CDT procedures. Our findings suggest that CDT should be considered in patients with upper thigh or pelvic DVT."

Dr. Tone Ronnaug Enden will present this study during the Late-Breaking Abstracts Session on Tuesday, December 13, at 7:30a.m. PST at the San Diego Convention Center in Hall AB.

SOURCE American Society of Hematology