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T J Schroeder

Publications and source records attributed to T J Schroeder.

At least 19 recordsLinked to original sources
PubMed1998

Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.

BACKGROUND: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS: A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

Acute Disease↗
PubMed1998

Utility of standardized histological classification in the management of acute rejection. 1995 Efficacy Endpoints Conference.

BACKGROUND: Standardized histological grading of transplant kidney biopsies has become a primary criterion for diagnosis of rejection in immunosuppression clinical trials. METHODS: A consortium of 19 transplant centers from North America, Europe, and Australia convened in 1995 to examine kidney transplant rejection. Data from the 1995 Efficacy Endpoints Conference were examined for frequency of adoption of Banff schema. Biopsy grading was correlated with clinical parameters of rejection and therapy response. RESULTS: Histological confirmation of rejection episodes occurred in 73% of 953 cases, with Banff criteria adoption increasing in frequency between 1992 and 1995. Banff grading significantly correlated with clinical rejection severity (rejection creatinine: grade I, 2.8+/-0.2 mg/dl; grade II, 3.5+/-0.2 mg/dl; grade III, 4.1+/-0.3 mg/dl; P < 0.001), although nadir creatinines were similar. Response rates of Banff grades I and II to steroid therapy were not different, but only 42% of grade III rejections responded to steroids (P < 0.003. Banff grading also correlated with postrejection creatinine, day 15: grade I, 2.2+/-0.2 mg/dl; grade II, 3.0+/-0.2 mg/dl; grade III, 3.8+/-0.4 mg/dl (P < 0.001), and day 30: grade I, 2.1+/-0.1 mg/dl; grade II, 2.2+/-0.2 mg/dl; grade III, 2.7+/-0.2 mg/dl (P < 0.06). Banff grade III correlated with reduced graft survival at 1 year: grade I, 86%; grade II, 88%; grade III, 70% (P < 0.01). CONCLUSIONS: This multicenter review of rejection severity confirms that standardized histologic classifications such as the Banff schema provide a reliable means for stratifying patient risk of treatment success or failure. These data support the use of Banff criteria in clinical trial design.

Acute Disease↗
PubMed1998

Efficacy Endpoints Conference on Acute Rejection in Kidney Transplantation: summary report of the database.

An international database of rejection episodes and their characteristics with regard to definition and follow-up parameters was developed to improve the approach to protocol development for clinical trials. Nineteen North American, European, and Australian centers uniformly reported on 50 consecutive transplant rejection episodes. Data collected included patient demographic parameters, induction and maintenance immunosuppression therapies, rejection agents (drug, dose, duration), clinical signs (50% decrease in urine, fever), serum creatinine (nadir, at rejection, daily during antirejection therapy to 15 days, and days 30, 90, 180, and 365 after rejection date), histopathological findings, morbidity, recurrence of rejection, and function at 1 year. The centers contributed a total of 953 presumed rejection episodes, of which 842 were confirmed as acute rejection episodes. The majority of cases were first rejections (81%), and rejection occurred 119 +/- 345 days following transplantation. The Banff Schema of histological grading was used in 38% of biopsy-proven rejection episodes (2% Borderline, 42% Grade I, 38% Grade II, 18% Grade III). Only 30% of all rejections showed clinical signs that were most likely to occur in Grade III rejection episodes (P < 0.006). The serum creatinine response was well below the rejection creatinine level by day 15 following initiation of antirejection therapy in the majority of cases. A significant number of the cases (34%) reported in this database experienced a recurrent rejection approximately 85 days following the first rejection. Graft survival 1 year following the rejection episode was good (83%). These findings will facilitate development of clinical trial design and beneficially impact approaches to antirejection therapies for kidney allograft recipients.

Acute Disease↗
PubMed1998

Proposed consensus for definitions and endpoints for clinical trials of acute kidney transplant rejection.

Progress in transplantation therapeutics requires validation from multicenter trials in which enrollment criteria and endpoint definitions have been standardized. A database of acute rejection was established from 19 North American, European, and Australian transplant centers and included parameters on rejection diagnosis and treatment of 50 consecutive rejection episodes from each center. Patient demographics, induction and maintenance immunosuppressive therapies, antirejection agents (drug, dose, duration), clinical signs (decrease in urine volume, presence of fever of > or =38.5 degrees C), serum creatinine concentration (nadir, at rejection, daily during antirejection therapy to 15 days, and days 30, 90, 180, and 365 after rejection date), rejection biopsy findings, morbidity, recurrence of rejection, and renal function at 1 year were recorded for 953 rejection episodes. From these data, three definitions were proposed. Acute rejection was defined as an immunologic process resulting in a serum creatinine increase of > or =0.4 mg/dL, with or without clinical signs, and should include a biopsy confirmation that has been standardized to the Banff criteria. Corticosteroid-resistant rejection was defined as a rejection episode in which a minimum of 250 to 1000 mg of methylprednisolone administered as initial therapy fails to result in stabilization or reduction of the serum creatinine after 3 days of corticosteroid treatment. Successful response to therapy was defined as a serum creatinine level < or =110% of the serum creatinine on the day of the rejection diagnosis and a return of the serum creatinine to or below the rejection creatinine level by 5 days of therapy with maintenance of this response for a minimum of 30 days. The work represented in the Efficacy Endpoints Database provides a step toward improving definitions in clinical trials. Continuity in clinical trial design should lead to improvements in evaluation of outcomes and, thereby have an effect on clinical practice.

Acute Disease↗
PubMed1998

Observations on recovery of renal function following treatment for acute rejection.

The characteristics of rejection and rejection response have not been systematically described in renal transplant recipients. The Efficacy Endpoints Conference Database contains characteristics from 953 episodes of rejection occurring at 19 North American, European, and Australian transplant centers. This database was used to profile renal transplant rejection episodes treated with primary steroid therapy, primary antilymphocyte antibody therapy, and rescue antilymphocyte antibody therapy. Primary steroid therapy was used in 88% of the rejection episodes. A successful response was more common in recipients without fever (72% v 61%; P < 0.004), in recipients experiencing less than a Banff Grade III rejection (92% v 75%; P = 0.009), and was more likely associated with graft function at 1 year following the rejection than rejection episodes that failed steroid therapy (89% v 82%; P = 0.013). Steroid success was statistically identifiable by day 2 of therapy and clinically useful by day 3; serum creatinine on these days of therapy is shown as a ratio of the rejection creatinine (102% v 112% day 1, success v failure, P< 0.002; 104% v122% day 2, success v failure, P < 0.0001; 105% v125% day 3, success vfailure, P < 0.0001). Response to primary antilymphocyte antibody therapy reached significance at day 5 of therapy when serum creatinine decreased below the rejection creatinine level in antilymphocyte successes but remained at or above the rejection creatinine in those who failed the therapy (90% v 135%; P < 0.01). For rescue antilymphocyte antibody therapy, a response was evident after 5 days of therapy (approximately day 9 to 10 of rejection) when serum creatinine began to decline and continued lower throughout the 10-day course of antilymphocyte antibody therapy (day 14 to 15 of rejection; serum creatinine 3.0 mg/dL v 4.4 mg/dL for success v failure; P < 0.004). Serum creatinine was lower throughout the first year following therapy in each success group (steroids, antilymphocyte antibody therapy as primary or as rescue), and a greater percentage of failures of any of the three therapies resulted in graft loss. Interestingly, 1-year graft survival was not different in the patients who were treated with antilymphocyte antibody therapy as primary than those who received these antirejection agents as rescue therapy (81% and 84%, respectively). The Efficacy Endpoints Conference Database provides an essential tool for profiling acute rejection in renal transplantation and should lead to improved evaluation of rejection therapies.

Acute Disease↗
PubMed1998

Comparison of two cyclosporine formulations in healthy volunteers: bioequivalence of the new Sang-35 formulation and Neoral.

This study was conducted to establish bioequivalence between a newly developed oral cyclosporine formulation, Sang-35 (SangStat Medical Corp., Menlo Park, CA), and the microemulsion formulation Neoral (Novartis Pharmaceuticals, East Hanover, NJ). In a randomized, open-label, two-way crossover study, 36 fasted, healthy male volunteers received a single 500-mg cyclosporine dose formulated either as Sang-35 or Neoral. Mean are under the concentration-time curve to infinity (AUC0-infinity) for Sang-35 was 13,900 microg x hr/L compared with 14,000 microg x hr/L for Neoral, with a 90% confidence interval (CI) of 96% to 103% for the geometric mean ratio of the two formulations. Mean maximum concentration (Cmax) was 1,690 microg/L for Sang-35 and 1,700 microg/L for Neoral, with a 90% CI of 96% to 103%. Geometric mean ratios for both AUC0-infinity and Cmax were within the acceptance criteria for bioequivalence (80-125%). Additional studies showed no differences between Sang-35 and Neoral after high-fat meals (n = 19), in female volunteers (n = 25) and in black volunteers (n = 7). It is concluded that single doses of the oral cyclosporine formulations Sang-35 and Neoral are bioequivalent in healthy fasted subjects, after high-fat meals, in women, and in blacks.

Administration, Oral↗