scholarly journals Fecal Microbial Transplantation versus Mesalamine Enema for Treatment of Active Left-Sided Ulcerative Colitis—Results of a Randomized Controlled Trial

2021 ◽  
Vol 10 (13) ◽  
pp. 2753
Author(s):  
Jan Březina ◽  
Lukáš Bajer ◽  
Pavel Wohl ◽  
Dana Ďuricová ◽  
Pavel Hrabák ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Controlled Trial ◽  
Chronic Inflammatory Disease ◽  
Study Endpoint ◽  
Primary Study ◽  
Aminosalicylic Acid ◽  
Open Label ◽  
Promising Alternative ◽  
Mayo Score ◽  
Primary Study Endpoint

Background and Aims: Ulcerative colitis (UC) is a chronic inflammatory disease. Fecal microbial transplantation (FMT) is a promising alternative treatment. Methods: This multicenter, open-label, noninferiority trial randomized patients with active left-sided UC (Mayo score 4–10) equally to FMT or 5-aminosalicylic acid (5-ASA) enemas. FMT enemas were administered five times in the first week and then once weekly for 5 weeks. 5-ASA enemas were administered daily for 2 weeks and then every other day. The primary study endpoint was clinical remission, with a total Mayo score ≤2 at week 12 with no subscore >1. Results: Sixty-one patients were screened; 45 were enrolled and randomized to FMT (n = 23) or 5-ASA (n = 22). Twenty-one FMT and 22 5-ASA patients completed at least the week 4 study visit and were included in the mITT analysis. Twelve FMT (57%) and eight 5-ASA patients achieved the primary study endpoint. FMT noninferiority with 10% margin was confirmed (95% CI: −7.6%, 48.9%). Adverse events occurred in 12 FMT (57%) and 13 5-ASA (59%) patients. Increased microbial diversity persisted 3 months after FMT. Conclusion: FMT is an effective treatment for left-sided UC and increased recipient microbiome diversity. Targeted microbiome modification may improve FMT efficacy. Further investigation is needed to guide donor and patient selection.

SIRFLOX: Differences in site of first progression between mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 ± bev + selective internal radiation therapy (SIRT) in first-line patients (pts) with metastatic colorectal cancer (mCRC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 637-637
Author(s):  
Peter Gibbs ◽  
Volker Heinemann ◽  
Navesh K. Sharma ◽  
Michael P. N. Findlay ◽  
Jens Ricke ◽  
...  
Keyword(s):  
Disease Progression ◽  
Hepatic Metastases ◽  
Study Endpoint ◽  
Primary Study ◽  
First Line ◽  
Open Label ◽  
Number Of Patients ◽  
Resin Microspheres ◽  
Primary Study Endpoint ◽  
Folfox Chemotherapy

637 Background: SIRFLOX, an international multi-centre open-label RCT in first-line pts with non-resectable, liver-only or liver-dominant mCRC, showed that compared to FOLFOX (± bev) chemotherapy alone [arm A] FOLFOX (± bev) plus SIRT using Y-90 resin microspheres [arm B] did not improve overall PFS (median 10.2 v 10.7 months arm A v B, HR: 0.93; 95% CI 0.77–1.12; p = 0.429). However, liver PFS by competing risk analysis was improved with the addition of SIRT (median 12.6 v 20.5 months in arm A v B, HR: 0.69; 95% CI 0.55–0.90; p = 0.002). The current analysis examines patterns of disease progression and potential impact on the primary study endpoint. Methods: Site and pattern (intra/extra-hepatic) of first progression, and whether progression was due to growth of existing lesions or the appearance of new lesions, was judged by an independent reader blinded to study arm. Results: From Oct 2006 to Apr 2013, 530 pts were randomised (arm A, n = 263; arm B, n = 267); 212 (40%) had extra-hepatic metastases at study entry; 292 (55%) were stratified to receive bev. As of 31 Jan 2015, the total number of patients with disease progression in arm A v B were 178 and 166, respectively. The site of first progression was more frequently in the liver (± other sites) in arm A v B (92.1% v 72.3%; p < 0.001). Conversely, site of first progression was less frequent in the lung (± other sites) in arm A v B (19.1% v 42.8%; p < 0.001). A higher proportion of first progression occurred in the liver alone in arm A v B (77.0% v 52.4%; p < 0.001). Conversely, a lower proportion of first progression occurred only in non-liver sites, primarily lung, in arm A v B (7.9% v 47.7%; p < 0.001). Of patients with first progression in the liver, a higher proportion occurred in existing liver lesions (± extrahepatic sites) in arm A v B (72.5% v48.2%; p < 0.001). Conclusions: The addition of SIRT to FOLFOX chemotherapy alone (± bev) reduced the frequency at which first disease progression occurred in the liver. Where first progression did occur in the liver, the addition of SIRT led to this more frequently being due to the appearance of lesions not evident on baseline imaging. Clinical trial information: NCT00724503.

scholarly journals Efficacy of 5-Aminosalicylic Acid Enemas in the Treatment of Distal Ulcerative Colitis

1990 ◽  
Vol 4 (7) ◽  
pp. 468-471 ◽  
Author(s):  
MG Robinson ◽  
DL Decktor
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
First Episode ◽  
High Dose ◽  
Aminosalicylic Acid ◽  
Open Label ◽  
Distal Ulcerative Colitis ◽  
The Mean

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.

scholarly journals DOP59 Maintenance of remission with tofacitinib in patients with ulcerative colitis: Updated results of a subpopulation analysis from an open-label, long-term extension study, OCTAVE Open

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S098-S099
Author(s):  
J F Colombel ◽  
M T Osterman ◽  
P Ibanez ◽  
A J Thorpe ◽  
H Zhang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Opportunistic Infections ◽  
Safety Data ◽  
Similar Efficacy ◽  
Major Adverse Cardiovascular Events ◽  
Open Label ◽  
Phase 3 ◽  
Vein Thrombosis ◽  
Mayo Score

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety were demonstrated in 3 Phase 3, randomised, placebo-controlled studies in patients with moderate to severe UC.1 An ongoing, Phase 3, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) included patients from OCTAVE Induction 1 and 2 and OCTAVE Sustain. Methods We present data (as of May 2019) from the ‘maintenance remission’ subpopulation in the OLE study who were in remission (total Mayo score ≤2, no individual subscore &gt;1, rectal bleeding subscore of 0) at Week 52 of OCTAVE Sustain (having received tofacitinib 5 or 10 mg twice daily [BID]). These patients received tofacitinib 5 mg BID as per protocol in the OLE study. Efficacy data up to Month 36 of the OLE study (as observed and with non-responder and last observation carried forward imputation [NRI-LOCF]) are presented for this subpopulation. Safety data are reported for all patients who received tofacitinib 5 mg BID in the OLE study. Results Of 944 patients receiving ≥1 dose of tofacitinib in the OLE study, 163 were in remission at Week 52 of OCTAVE Sustain (mean age 45 years; 46.0% female). Of these, 66 (40.5%) and 76 (46.6%) received tofacitinib 5 and 10 mg BID, respectively, in OCTAVE Sustain, and 21 (12.9%) received a placebo. In total, 67/163 (41.1%) patients discontinued the OLE study, 16 (9.8%) due to adverse events (AEs) excl. worsening UC and 15 (9.2%) due to insufficient clinical response. Among patients that continued, efficacy (Table) was maintained over 36 months and was similar irrespective of the dose received in OCTAVE Sustain. Of 175 patients who received tofacitinib 5 mg BID (incl. 163 from the maintenance remission subpopulation), 152 (86.9%), 33 (18.9%) and 20 (11.4%) had AEs, serious AEs and severe AEs, respectively. The most frequent treatment-emergent AEs (TEAEs) were worsening UC (41 patients, 23.4%) and nasopharyngitis (38 patients, 21.7%). Six (3.4%) patients receiving tofacitinib 5 mg BID had serious infections, 11 (6.3%) had herpes zoster (non-serious and serious), 4 (2.3%) had opportunistic infections, 2 (1.1%) had major adverse cardiovascular events and 5 (2.9%) had malignancy (excl. non-melanoma skin cancer). No deep vein thrombosis, pulmonary embolism or deaths were reported in patients receiving tofacitinib 5 mg BID. Conclusion Most patients in remission at Week 52 of OCTAVE Sustain maintained efficacy with tofacitinib 5 mg BID over 36 months in the OLE study. Similar efficacy was observed for patients whose dose was reduced from tofacitinib 10 mg BID in OCTAVE Sustain to 5 mg BID in the OLE study, vs. those who received 5 mg BID throughout both OCTAVE Sustain and the OLE study. No new safety risks were identified. Reference

scholarly journals Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Kazuki Kakimoto ◽  
Minoru Matsuura ◽  
Takumi Fukuchi ◽  
Hitoshi Hongo ◽  
Tsuguhiro Kimura ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trial ◽  
Exploratory Study ◽  
Response Rate ◽  
Mucosal Healing ◽  
Prospective Clinical Trial ◽  
Aminosalicylic Acid ◽  
Open Label ◽  
Steroid Dependent ◽  
Adsorptive Apheresis

Abstract Background Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. Methods We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. Results The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. Conclusions GMA shows effectiveness in inducing remission in UC patients not receiving steroid.

scholarly journals Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e037306
Author(s):  
Julien Hogan ◽  
Aubriana Perez ◽  
Anne-Laure Sellier-Leclerc ◽  
Isabelle Vrillon ◽  
Francoise Broux ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Side Effects ◽  
Controlled Trial ◽  
Primary Study ◽  
Childhood Onset ◽  
Open Label ◽  
Substantial Impact ◽  
Frequently Relapsing Nephrotic Syndrome ◽  
Steroid Dependent

IntroductionGuidelines for the treatment of steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS) are lacking. Given the substantial impact of SDNS/FRNS on quality of life, strategies aiming to provide long-term remission while minimising treatment side effects are needed. Several studies confirm that rituximab is effective in preventing early relapses in SDNS/FRNS; however, the long-term relapse rate remains high (~70% at 2 years). This trial will assess the association of intravenous immunoglobulins (IVIgs) to rituximab in patients with SDNS/FRNS and inform clinicians on whether IVIg’s immunomodulatory properties can alter the course of the disease and reduce the use of immunosuppressive drugs and their side effects.Methods and analysisWe conduct an open-label multicentre, randomised, parallel group in a 1:1 ratio, controlled, superiority trial to assess the safety and efficacy of a single infusion of rituximab followed by IVIg compared with rituximab alone in childhood-onset FRNS/SDNS. The primary outcome is the occurrence of first relapse within 24 months. Patients are allocated to receive either rituximab alone (375 mg/m²) or rituximab followed by IVIg, which includes an initial Ig dose of 2 g/kg, followed by 1.5 g/kg injections once a month for the following 5 months (maximum dose: 100 g).Ethics and disseminationThe study has been approved by the ethics committee (Comité de Protection des Personnes) of Ouest I and authorised by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé). Results of the primary study and the secondary aims will be disseminated through peer-reviewed publications.Trial registration numberNCT03560011.

Effect of Cotherapy Reduction on Tolerability of Epilepsy Add-On Therapy: A Randomized Controlled Trial

2005 ◽  
Vol 39 (3) ◽  
pp. 418-423 ◽  
Author(s):  
Dean K Naritoku ◽  
Joseph F Hulihan ◽  
Lesley Kraut Schwarzman ◽  
Marc Kamin ◽  
William H Olson
Keyword(s):  
Adverse Events ◽  
Dose Group ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Primary Study ◽  
Open Label ◽  
Open Label Study ◽  
Effective Doses ◽  
Receive Treatment ◽  
To Receive

BACKGROUND: Adverse effects are the most common cause for failure of an antiepileptic drug (AED), especially when an AED is added to existing therapy. With the increased drug load, it may not be possible to titrate the newly added AED to effective doses. Reducing the dosage of AED cotherapy as the new drug is introduced may improve tolerability. OBJECTIVE: To evaluate reduction of AED cotherapy as a strategy to improve tolerability and patient retention when a new AED is added to existing therapy. METHODS: In a 20-week, randomized, open-label study, topiramate was initiated as add-on therapy in adults and adolescents (⩾12 y of age) with inadequately controlled partial-onset seizures. Patients were randomized to receive treatment in which adverse events could be managed by adjustments in AED cotherapy (flex-dose group) or treatment in which AED cotherapy dosages remained fixed (fixed-dose group). Topiramate could be adjusted as needed in both groups. In the flex-dose group, patients exited randomized treatment when topiramate was discontinued. In the fixed-dose group, patients exited when AED cotherapy was reduced due to adverse events or when topiramate was discontinued. The primary study outcome was the percentage of patients exiting randomized treatment due to adverse events. RESULTS: The flex-dose group comprised 297 patients; 302 patients were in the fixed-dose group. Significantly fewer patients in the flex-dose group exited the study due to adverse events (16% vs 23% in the fixed-dose group; p = 0.02). In the flex-dose group, 10% (17 of 168) of patients discontinued topiramate due to adverse events after AED cotherapy was reduced versus 22% (29 of 129) when AED cotherapy was not reduced. CONCLUSIONS: Reduction of AED cotherapy is a useful strategy to improve tolerability and retention when topiramate is initiated as adjunctive therapy.

scholarly journals Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1141-1145 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Francis J. Giles ◽  
Kapil N. Bhalla ◽  
Javier Pinilla-Ibarz ◽  
Richard A. Larson ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Molecular Response ◽  
Open Label ◽  
Imatinib Resistance ◽  
Abl Tyrosine Kinase

Abstract Nilotinib is a potent selective inhibitor of the BCR-ABL tyrosine kinase approved for use in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP), and in CML-CP and CML-accelerated phase after imatinib failure. Nilotinib (400 mg twice daily) was approved on the basis of the initial results of this phase 2 open-label study. The primary study endpoint was the proportion of patients achieving major cytogenetic response (CyR). All patients were followed for ≥ 24 months or discontinued early. Of 321 patients, 124 (39%) continue on nilotinib treatment. Overall, 59% of patients achieved major CyR; this was complete CyR (CCyR) in 44%. Of patients achieving CCyR, 56% achieved major molecular response. CyRs were durable, with 84% of patients who achieved CCyR maintaining response at 24 months. The overall survival at 24 months was 87%. Adverse events were mostly mild to moderate, generally transient, and easily managed. This study indicates that nilotinib is effective, with a manageable safety profile, and can provide favorable long-term benefits for patients with CML-CP after imatinib failure. This trial was registered at www.clinicaltrials.gov as #NCT00109707.

Phase II study of sunitinib administered in a continuous daily dosing regimen in patients (pts) with advanced GIST

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9532-9532 ◽  
Author(s):  
S. George ◽  
P. G. Casali ◽  
J. Blay ◽  
A. Le Cesne ◽  
A. R. Tyler ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Kinase Inhibitor ◽  
Continuous Treatment ◽  
Study Endpoint ◽  
Primary Study ◽  
Open Label ◽  
Early Results ◽  
Imatinib Resistant ◽  
Grade 3

9532 Background: Sunitinib malate (SU11248) is an oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities due to inhibition of KIT, VEGFRs, PDGFRs, RET, and FLT3. In previous phase I/II and III trials in pts with imatinib-resistant GIST, sunitinib demonstrated efficacy and favorable clinical tolerability when administered in 6-week treatment cycles consisting of 4 weeks sunitinib (50 mg QD), followed by 2 weeks off treatment. The current study examined continuous sunitinib dosing as a way to avoid potential reactivation of tumor cells during the off-treatment period. Methods: This open-label, multicenter, phase II trial was designed to evaluate the efficacy, safety, and tolerability of sunitinib administered once daily using a continuous-treatment regimen in pts with imatinib-resistant GIST. Treatment is initiated with 37.5 mg sunitinib daily, with the option to titrate dosing on an individual basis depending on tolerability. The primary study endpoint is clinical benefit rate, defined as percent of evaluable pts with confirmed CR, PR, or SD ≥24 weeks using RECIST. Secondary endpoints included ORR, TTP, PFS, OS, and safety/tolerability measures. Results: Of 28 pts who had started treatment at the time of this analysis, early results were available for 17 pts from two centers. The most commonly occurring treatment-related adverse events were stomatitis, hand-foot syndrome, gastroesophageal reflex, and fatigue, which were generally grade 1. Two pts experienced treatment-related grade 3 hypertension, and another exhibited grade 3 asymptomatic neutropenia. Five pts have been evaluated for benefit after 8 weeks of treatment. Stable disease (which is the clinical benefit typically observed in GIST pts treated with sunitinib) was demonstrated in all five pts. Expanded safety/tolerability and efficacy results will be available for presentation. Conclusions: Continuous dosing of sunitinib is feasible and appears to be associated with acceptable tolerability in pts with imatinib-refractory GIST, similar to the extensive experience documented with intermittent sunitinib dosing. It is possible that continuous daily dosing of sunitinib may further improve the outcomes of pts with GIST. [Table: see text]

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