Long-Term Safety and Efficacy Data on Childhood Venous Thrombosis Treated with Enoxaparin: An Open Label Survey of Once-Daily Versus Twice-Daily Administration.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 549-549
Author(s):  
Ulrike Nowak-Gottl ◽  
Christine During ◽  
Christoph Bidlingmaier ◽  
Nick Merkel ◽  
Rosemarie Schobess
Keyword(s):  
Efficacy And Safety ◽  
Open Label ◽  
Once Daily ◽  
Randomised Study ◽  
Catchment Areas ◽  
Prothrombotic Risk Factors ◽  
The Individual ◽  
A Minor

Abstract Low molecular weight heparin is as effective as unfractionated heparin for treatment of venous thromboembolism (VT) in adults, and it has been recently demonstrated that once-daily (q24h) or twice-daily (q12h) enoxaparin (E) administration had no impact on safety (bleeding rate) of efficacy (re-thrombosis rate) in the treatment of acute VT. However, in this setting it is still unclear for children, if enoxaparin should be administered q24h or q12h. In this open label pilot safety study 75 children > the neonatal period, enrolled from two different catchment areas of Germany were treated with E with a target 2–4 h anti Xa activity between 0.4 – 0.8 IU/ml. After the acute thrombotic onset during which E was administered q12h for a median (range) period of 7 (1–14) days, based on the individual decision of the study centres stratification into the study arms once-daily versus twice daily was performed. Enoxaparin was administered in both study centres regardless of age at DVT-onset, thrombus burden, underlying basic diseases or presence of prothrombotic risk factors. No difference was observed between the stratifications performed in the study centres (p=0.5). Median (range) dose administered q24h (n=50) or q12h (n=25) in children with DVT was 1.2 mg/kg (0.5–3.0) respectively. Median (range) treatment duration was 5 months (1–13). Prospectively defined study endpoints were adverse effects, e.g. re-thrombosis, bleeding, and therapy-related death. Median follow-up time was 24 months. No significant differences were found between the two patient groups treated with respect to anti Xa activities, efficacy and safety. Further statistical analysis performed to evaluate the overall differences between q24h and q12h E administration again revealed no significant differences for the study endpoints: Re-thrombosis occurred in two patients each (p=0.6), and a minor subdural bleeding was diagnosed in one patient treated q12h (p=0.4). During the follow-up no major bleeding or therapy-related death was observed. In conclusion, data presented here give evidence that long-term enoxaparin administration within the reported target anti Xa activity for treatment of childhood VT has a good efficacy and safety profile when administered q24h. These data have to be confirmed in a multicentre randomised study.

O-132 Sustained efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT 52-week data

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S As-Sanie ◽  
L Giudice ◽  
M S Abrao ◽  
K Wilk ◽  
C Mehedintu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Efficacy And Safety ◽  
Mineral Density ◽  
Open Label ◽  
Substantial Impact ◽  
Once Daily ◽  
Sustained Improvement ◽  
Pain Domain ◽  
Extension Period

Abstract Study question To assess the long-term (52-week) efficacy and safety of relugolix combination therapy (Relugolix-CT) in the treatment of endometriosis-associated pain. Summary answer Relugolix-CT demonstrated a sustained improvement of endometriosis-associated pain and maintenance of bone mineral density (BMD) over the extension treatment period. It was well tolerated. What is known already Endometriosis is a chronic condition characterized by symptoms of menstrual and non-menstrual pain, and dyspareunia, which have a substantial impact on women’s lives. SPIRIT 1 and 2 were Phase 3, randomized, double-blind, placebo-controlled studies of once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in premenopausal women (age 18–50 years) with surgically diagnosed endometriosis and moderate-to-severe dysmenorrhea and non-menstrual pelvic pain (NMPP) at baseline. These trials demonstrated a significant improvement of dysmenorrhea, NMPP and dyspareunia in women treated with Relugolix-CT, with a minimal decline in BMD vs placebo over 24 weeks. Study design, size, duration Women who completed the 24-week pivotal studies (SPIRIT 1 and 2 trials) were eligible to enroll in an open-label, single-arm, long-term safety and efficacy extension study for an additional 80 weeks. All women received once-daily oral Relugolix-CT. Analyses were done based on original randomization in pivotal studies: Relugolix-CT, delayed Relugolix-CT (relugolix 40 mg alone for 12 weeks, then Relugolix-CT for 12 weeks), or placebo. Here, 52-week efficacy and safety outcomes are presented. Participants/materials, setting, methods The primary endpoints were the proportion of dysmenorrhea and NMPP responders at Week 52, based on daily Numerical Rating Scale (NRS) scores (0=no pain, 10=worst pain imaginable). A responder was a woman who achieved a predefined, clinically meaningful reduction from baseline in NRS score with no increase in analgesic use. Secondary efficacy endpoints included change in Endometriosis Health Profile-30 (EHP-30) pain domain scores, and analgesic/opioid use. Safety endpoints included adverse events (AEs) and BMD evaluation. Main results and the role of chance Of 1261 randomized patients, 1044 completed the primary studies; 802 enrolled in the long-term extension and 681 completed 52 weeks of treatment. Baseline demographics and clinical characteristics of the extension population were consistent with those of the original randomized population. Sustained improvement of endometriosis-associated pain was demonstrated with Relugolix-CT through 52 weeks, the proportion of responders for dysmenorrhea was 84.8% and 73.3% for NMPP. NRS least squares (LS) mean scores for dysmenorrhea and NMPP decreased from 7.4 (severe) and 6.0 (moderate) at SPIRIT study baseline to 1.3 (mild) and 2.2 (mild) at Week 52, equating to 82.8% and 62.9% reduction in dysmenorrhea and NMPP, respectively. Mean NRS for dyspareunia decreased from 5.9 (moderate) to 2.4 (mild), demonstrating 60.1% reduction with Relugolix-CT. Daily functioning measured by the EHP-30 pain domain score was improved (–38.1 point) and the majority of women (85.6%) were opioid-free at Week 52. There was no disproportionate increase in the incidence of AEs in the Relugolix-CT group with no new safety signals identified through the 52 weeks. BMD was preserved over the extension period with overall LS mean change from baseline to Week 52 of –0.83% (95% CI: –1.34, –0.32) for lumbar spine in the Relugolix-CT group. Limitations, reasons for caution The study was conducted as an open-label study without a control group over the 28 weeks of the extension period. Wider implications of the findings Relugolix-CT demonstrated a sustained improvement of dysmenorrhea, NMPP, and dyspareunia, and reduced pain-related functional limitations and the need for opioids over 52 weeks in women with moderate-to-severe endometriosis-associated pain. Relugolix-CT was generally well tolerated and associated with minimal BMD loss after treatment initiation followed by BMD maintenance over 52 weeks. Trial registration number NCT03654274

Long-Term Outcomes in Patients With BRAF V600–Mutant Metastatic Melanoma Who Received Dabrafenib Combined With Trametinib

2018 ◽  
Vol 36 (7) ◽  
pp. 667-673 ◽  
Author(s):  
Georgina V. Long ◽  
Zeynep Eroglu ◽  
Jeffrey Infante ◽  
Sapna Patel ◽  
Adil Daud ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Combination Therapy ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Mek Inhibitor ◽  
Efficacy And Safety ◽  
Once Daily ◽  
Free Survival

Purpose To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600–mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods BRAF inhibitor–naive patients with BRAF V600–mutant MM were randomly assigned 1:1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with ≥ 5 years of follow-up. Results As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24%] of 54 enrolled at this dose plus five [11%] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30%; 5 years, 28%) and progression-free survival (4 and 5 years, both 13%) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45%) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51%). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed. Conclusion This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600–mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last ≥ 5 years in some patients with MM.

scholarly journals Open-Label Follow-Up of the PEPITES Study (PEOPLE) to Evaluate the Long-Term Efficacy and Safety of Epicutaneous Peanut Immunotherapy in Peanut-Allergic Children

2020 ◽  
Vol 145 (2) ◽  
pp. AB141
Author(s):  
David Fleischer ◽  
Gordon Sussman ◽  
Kirsten Beyer ◽  
Jonathan Hourihane ◽  
Roxanne Oriel ◽  
...  
Keyword(s):  
Efficacy And Safety ◽  
Open Label ◽  
Term Efficacy

Upfront azacitidine (AZA) in juvenile myelomonocytic leukemia (JMML): Interim analysis of the prospective AZA-JMML-001 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10031-10031
Author(s):  
Charlotte M. Niemeyer ◽  
Christian Flotho ◽  
Daniel B. Lipka ◽  
Jan Starý ◽  
Claudia Rössig ◽  
...  
Keyword(s):  
Juvenile Myelomonocytic Leukemia ◽  
Open Label ◽  
Historical Cohort ◽  
Hematopoietic Stem ◽  
Once Daily ◽  
Curative Therapy ◽  
Retrospective Comparison ◽  
Myelomonocytic Leukemia

10031 Background: Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for JMML patients (pts). Novel therapies controlling the disorder prior to HSCT are urgently needed. A phase 2, multicenter, open-label study was conducted to evaluate safety and anti-leukemia activity of AZA monotherapy prior to HSCT in pts with newly diagnosed (ND) JMML. Methods: AZA (75 mg/m2 IV) was administered once daily on days 1–7 of each 28-day cycle (C). Primary endpoint was number of pts with clinical complete remission or clinical partial remission (cPR) at C3 day (D) 28 (C3D28). Results: 18 JMML pts (13 PTPN11-, 3 NRAS-, 1 KRAS-, 1 NF1-mutated) were enrolled from 09/2015 to 11/2017. Median (range) white blood cell and platelet (Plt) counts were 19.7 (4.3–59.0) × 109/L and 28 (7–85) × 109/L, respectively. DNA methylation class (MC) was high, intermediate (int), or low in 11, 5, and 2 pts, respectively. 16 pts completed C3 and 5 pts C6. 2 pts discontinued treatment (Tx) pre-C3D28 due to disease progression (PD). 6 pts (33%) had ≥ 1 grade (Gr) 3–4 manageable adverse event (AE) related to AZA. Most common Gr 3–4 AEs related to AZA were neutropenia (2) and anemia (2). 11 pts (61%) were in cPR at C3D28; 7 had PD at C3D28 or prior. All 7 pts of the int/low MC and 4/11 in high MC achieved cPR. 17 pts received HSCT at median of 58 days (37–518) from last AZA dose; 14 were leukemia-free at a median follow-up of 15.7 months (0.1–31.7) after HSCT. 2 pts (high MC) given HSCT relapsed after allograft. 16/18 pts were alive at a median follow-up of 19.8 months (2.6–37.3) from diagnosis. 1 pt discontinuing Tx prior to C3 died from PD; 1 non-responder died from transplant-related causes. Plt response in pts with cPR prompted retrospective comparison of Plt counts at time of HSCT with a historical registry control cohort. Pts with NF1-mutated JMML with higher Plt counts versus other genetic subtypes were excluded. While 7/16 (44%) study pts had Plt counts ≥ 100 × 109/L at HSCT, only 10/58 (17%) historical cohort pts reached this cutoff ( P < 0.01). Conclusions: This study shows that AZA monotherapy was well tolerated in pts with ND JMML. Although the long-term advantage of AZA Tx remains to be fully assessed, responses show it was effective in JMML and provided clinical benefit to pts in this study. Clinical trial information: NCT02447666.

scholarly journals Efficacy and Safety of Once-Weekly Thyroxine for Thyroxine-Resistant Hypothyroidism

2019 ◽  
Vol 3 (12) ◽  
pp. 2184-2193 ◽  
Author(s):  
Chellama Jayakumari ◽  
Abilash Nair ◽  
Jabbar Puthiyaveettil Khadar ◽  
Darvin V Das ◽  
Nandini Prasad ◽  
...  
Keyword(s):  
Term Treatment ◽  
Efficacy And Safety ◽  
Poor Control ◽  
Open Label ◽  
Thyroxine Therapy ◽  
Real World Setting ◽  
Long Term Treatment ◽  
Lost To Follow Up

Abstract Context Noncompliance with thyroxine therapy is the most common cause of poor control of hypothyroidism. An open-label prospective study to compare once-weekly thyroxine (OWT) with standard daily thyroxine (SDT) was undertaken. Design Patients taking thyroxine doses of >3 μg/kg/d, with or without normalization of TSH, were included and administered directly observed OWT or nonobserved SDT according to patient preference based on their weight for 6 weeks. Furthermore, patients on OWT were advised to continue the same at home without supervision. Results Twenty six of 34 patients on OWT and 7 of 18 patients on SDT achieved a TSH <10 μIU/mL (P < 0.05), and 2 patients from the SDT arm were lost to follow-up. During home treatment, 15 of 25 at 12 weeks and 19 of 23 contactable patients at a median follow-up of 25 months maintained TSH below target. Thyroxine absorption test was unable to predict normalization of TSH at 6 weeks of OWT therapy. No adverse events were seen with OWT-treated patients over the 12-week follow-up period. OWT has significantly higher efficacy (OR = 5.1) than SDT for patients with thyroxine-resistant hypothyroidism and is not associated with side effects. Conclusion OWT benefits a majority of patients in the long-term treatment of thyroxine-resistant hypothyroidism, in the real-world setting.

scholarly journals Efficacy and Safety of Daflon® in the Treatment of Idiopathic Epistaxis

2018 ◽  
Vol 33 (1) ◽  
pp. 62-68 ◽  
Author(s):  
Tamer M. Attia
Keyword(s):  
Emergency Room ◽  
Study Groups ◽  
Control Group ◽  
Efficacy And Safety ◽  
Open Label ◽  
Vascular Effects ◽  
Number Of Patients ◽  
Idiopathic Epistaxis

Background Epistaxis is a very common ENT emergency with the idiopathic variety being the commonest type. Daflon® is a mixture of flavonoids with beneficial vascular effects that may help in the treatment of epistaxis. Objective To assess the efficacy and safety of Daflon® in the treatment of idiopathic epistaxis. Methods This is an open-label randomized clinical trial conducted on patients with idiopathic epistaxis comparing 1 group receiving Daflon® for 1 month and a second group receiving Daflon® for 3 months with a control group receiving nothing. The groups were evaluated regarding the number of visits to an emergency room and the number of patients needing cautery as indicators for the control of epistaxis. Also, the severity of epistaxis was assessed using epistaxis severity score (ESS) before and after treatment. We followed the patients for 1 year to determine the long-term effect of both drug protocols. Results The study included 450 patients distributed equally among the 3 study groups. The administration of Daflon® whether for 1 month or 3 months resulted in a significant improvement in our indicators for control of epistaxis including the number of patients visiting an emergency room and those needing cauterization after the failure of light nasal packing when compared with control group. Also, the severity of epistaxis as defined by the ESS was significantly less at the end of each treatment period and at 1-year follow-up when compared with the pretreatment severity. However, the use of Daflon® for 3 months was associated with a significantly more epistaxis control at 1-year follow-up when compared with the 1-month administration. Conclusion Daflon® is a very effective and safe method for controlling idiopathic epistaxis. However, the daily use of Daflon® for 3 months has a more significant long-term beneficial effect than 1 month of use.

scholarly journals Long-term efficacy and safety of alemtuzumab in patients with RRMS: 12-year follow-up of CAMMS223

2020 ◽  
Vol 267 (11) ◽  
pp. 3343-3353 ◽  
Author(s):  
Brian Steingo ◽  
◽  
Yaser Al Malik ◽  
Ann D. Bass ◽  
Regina Berkovich ◽  
...  
Keyword(s):  
Disease Activity ◽  
Efficacy And Safety ◽  
Open Label ◽  
Disease Modifying Therapies ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Scale Scores ◽  
Treatment Naïve

Abstract Background In the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in treatment-naive patients with relapsing–remitting MS. Here, we assess efficacy and safety of alemtuzumab over 12 years in CAMMS223 patients who enrolled in the CAMMS03409 extension (NCT00930553), with available follow-up through the subsequent TOPAZ extension (NCT02255656). Methods In CAMMS223, patients received 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days); 22% received a third course. In the open-label, nonrandomized extensions, patients could receive as-needed additional alemtuzumab or other disease-modifying therapies. Results Of 108 alemtuzumab-treated patients in CAMMS223, 60 entered the CAMMS03409 extension; 33% received a total of 2 alemtuzumab courses, and 73% received no more than 3 courses through Year 12. Over 12 years, annualized relapse rate was 0.09, 71% of patients had stable or improved Expanded Disability Status Scale scores, and 69% were free of 6-month confirmed disability worsening. In Year 12, 73% of patients were free of MRI disease activity. Cumulatively throughout the extensions (Years 7–12), 34% of patients had no evidence of disease activity. Adverse event (AE) incidence declined through Year 12. Infusion-associated reactions peaked at first course and declined thereafter. Cumulative thyroid AE incidence was 50%; one immune thrombocytopenia event occurred, and there were no autoimmune nephropathy cases. Conclusions Alemtuzumab efficacy was maintained over 12 years in CAMMS223 patients, with 73% receiving no more than three courses. The safety profile in this cohort was consistent with other alemtuzumab clinical trials.

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