Open Label Trial of Add on Lacosamide Versus High Dose Levetiracetam Monotherapy in Patients With Breakthrough Seizures

Abstract DDAVP is effective treatment for VWD patients with adequate biologic response to administration of a trial dose. Intranasal therapy offers the advantage of ease of administration. Few prospective data evaluating response to intranasal DDAVP exist, especially in less common types such as type 2M VWD. As part of a study of a large Amish kindred of VWD in Northern Indiana, we conducted a prospective open label trial to assess response rate to a single dose of high concentration intranasal DDAVP in 11 affected individuals. Stimate® Nasal Spray (1.5 mg/ml) with weight based dosing was used. Laboratory parameters obtained prior to and 90 minutes after administration of Stimate® to assess for response included ristocetin cofactor activity (VWF:RCo), factor VIII activity(VIII:C), and VWF antigen (VWF:Ag) values. VWF:RCo ≥ 40% at 90 minutes post Stimate® administration was defined as adequate response. Of 212 evaluated members, 54 affected members were identified as defined by abnormally low VWF levels (VWF:RCo levels <35%) and confirmed by presence of C-to-T transition at nucleotide 4120 in exon 28 of the VWF gene. Multimer analysis in a subset of the affected individuals showed a normal pattern. Eleven adult Amish patients (5 males, 6 females), ranging in age from 20 to 56 years, were enrolled. Baseline VWF:RCo values ranged from 10% to 14%. Ten patients reported no active bleeding symptoms at the time of initiation of the trial, while one had ongoing problems with gingival bleeding. All patients weighed >50 kg; hence two intranasal Stimate® spray puffs were administered to each patient. Five of eleven patients had response to intranasal DDAVP as evidenced by ≥ 40% VWF:RCo levels 90 minutes after receiving Stimate® (Response range: 4.0 fold to 4.86 fold rise). The remaining patients did not meet definition of response (Response range: 1.6 fold to 3.8 fold rise). There were no major adverse effects. Nine patients had mild facial flushing alone; one patient had flushing and headache; one patient was asymptomatic. After Stimate® administration, the patient with gingival bleeding reported complete cessation of bleeding sustained for 24 hours. This is the first and largest report to date assessing response to intranasal DDAVP therapy in 2M VWD patients. High concentration intranasal DDAVP may be used for minor bleeding episodes in those patients with adequate response to a trial dose. It is easily self administered as home based first line hemostatic therapy. Intranasal DDAVP is well tolerated with minimal adverse effects. Prospective clinical correlation of efficacy is underway in this population. RESULTS OF STIMATE® TESTING AGE/SEX BASELINE FVIII:C (%) BASELINE VWF:AG(%) BASELINE VWF:RCO(%) 90 MINUTE FVIII:C(%) 90 MINUTE VWF:AG(%) 90 MINUTE VWF:RCO(%) 56/M 62 30 11 164 78 42 25/M 52 30 <10 182 111 48 47/M 57 31 14 196 108 68 27/M 46 20 <10 114 55 28 48/F 66 29 12 89 38 20 25/M 35 19 11 156 93 52 41/F 54 23 <10 106 56 35 20/F 27 15 <10 96 52 40 24/F 27 12 <10 91 49 24 20/F 34 19 <10 146 16 38 34/F 42 16 <10 112 58 24

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Once‐Daily, High‐Dose Levofloxacin versus Ticarcillin‐Clavulanate Alone or Followed by Amoxicillin‐Clavulanate for Complicated Skin and Skin‐Structure Infections: A Randomized, Open‐Label Trial

Clinical Infectious Diseases ◽

10.1086/341026 ◽

2002 ◽

Vol 35 (4) ◽

pp. 381-389 ◽

Cited By ~ 68

Author(s):

Donald R. Graham ◽

David A. Talan ◽

Ronald L. Nichols ◽

Christopher Lucasti ◽

Michael Corrado ◽

...

Keyword(s):

High Dose ◽

Open Label ◽

Once Daily ◽

Skin Structure ◽

Complicated Skin ◽

Amoxicillin Clavulanate ◽

Open Label Trial

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Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial

Journal of Clinical Oncology ◽

10.1200/jco.2010.31.4310 ◽

2011 ◽

Vol 29 (4) ◽

pp. 369-377 ◽

Cited By ~ 401

Author(s):

Alan K. Burnett ◽

Robert K. Hills ◽

Donald Milligan ◽

Lars Kjeldsen ◽

Jonathan Kell ◽

...

Keyword(s):

Prognostic Index ◽

Gemtuzumab Ozogamicin ◽

High Dose ◽

Open Label ◽

Younger Patients ◽

Significant Survival ◽

Trial Testing ◽

Risk Patients ◽

Open Label Trial ◽

To Receive

Purpose Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients. Patients and Methods In this open-label trial, 1,113 patients, predominantly younger than age 60 years, were randomly assigned to receive a single dose of GO (3 mg/m2) on day 1 of induction course 1 with one of the following three induction schedules: daunorubicin and cytarabine; cytarabine, daunorubicin, and etoposide; or fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin. In remission, 948 patients were randomly assigned to GO in course 3 in combination with amsacrine, cytarabine, and etoposide or high-dose cytarabine. The primary end points were response rate and survival. Results The addition of GO was well tolerated with no significant increase in toxicity. There was no overall difference in response or survival in either induction of consolidation. However, a predefined analysis by cytogenetics showed highly significant interaction with induction GO (P = .001), with significant survival benefit for patients with favorable cytogenetics, no benefit for patients with poor-risk disease, and a trend for benefit in intermediate-risk patients. An internally validated prognostic index identified approximately 70% of patients with a predicted benefit of 10% in 5-year survival. Conclusion A substantial proportion of younger patients with AML have improved survival with the addition of GO to induction chemotherapy with little additional toxicity.

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