Dataset Information

An open-label, randomized controlled trial of sulfamethoxazole-trimethoprim for Pneumocystis prophylaxis: results of 52-week follow-up.

ABSTRACT: Objectives:The aim was to investigate the long-term prophylactic efficacy, drug retention and safety of low-dose sulfamethoxazole-trimethoprim (SMX/TMP) prophylaxis against Pneumocystis pneumonia (PCP). Methods:Adult patients with rheumatic diseases receiving prednisolone ?0.6?mg/kg/day were randomized into the single-strength group (SS; SMX/TMP 400/80?mg daily), the half-strength group (HS; 200/40?mg daily) or the escalation group (ES; starting at 40/8?mg and increasing incrementally to 200/40?mg daily) and treated for 24?weeks, then observed for 52?weeks. The primary endpoint, the PCP non-incidence rate (non-IR) at week?24, has been reported previously. The secondary endpoints were the PCP non-IR at week?52, treatment discontinuation rate and adverse events. Results:Fifty-eight, 59 and 55 patients in the SS, HS and ES, respectively, received SMX/TMP. PCP did not develop in any of the patients by week?52. The estimated PCP non-IR in patients receiving SMX/TMP 200/40?mg daily (HS and ES) was 96.8-100%. Throughout the 52-week observation period, the overall discontinuation rate was significantly lower in HS than in SS (22.7 vs 47.2%, P?=?0.004). The discontinuation rates attributable to adverse events were significantly lower in HS (19.1%, P?=?0.007) and ES (20.3%, P?=?0.007) than in SS (41.8%). The IRs of adverse events requiring SMX/TMP dose reduction before week?52 differed among the three groups, with a significantly higher IR in SS than in HS or ES (P?=?0.007). Conclusion:SMX/TMP 200/40?mg had a high PCP prevention rate and was superior to SMX/TMP 400/80?mg in terms of drug retention and safety. Trial registration:University Hospital Medical Information Network Clinical Trials Registry, UMIN000007727.

SUBMITTER: Utsunomiya M

PROVIDER: S-EPMC7585401 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An open-label, randomized controlled trial of sulfamethoxazole-trimethoprim for <i>Pneumocystis</i> prophylaxis: results of 52-week follow-up.

Utsunomiya Masako M Dobashi Hiroaki H Odani Toshio T Saito Kazuyoshi K Yokogawa Naoto N Nagasaka Kenji K Takenaka Kenchi K Soejima Makoto M Sugihara Takahiko T Hagiyama Hiroyuki H Hirata Shinya S Matsui Kazuo K Nonomura Yoshinori Y Kondo Masahiro M Suzuki Fumihito F Nawata Yasushi Y Tomita Makoto M Kihara Mari M Yokoyama-Kokuryo Waka W Hirano Fumio F Yamazaki Hayato H Sakai Ryoko R Nanki Toshihiro T Koike Ryuji R Miyasaka Nobuyuki N Harigai Masayoshi M

Rheumatology advances in practice 20200706 2

<h4>Objectives</h4>The aim was to investigate the long-term prophylactic efficacy, drug retention and safety of low-dose sulfamethoxazole-trimethoprim (SMX/TMP) prophylaxis against <i>Pneumocystis</i> pneumonia (PCP).<h4>Methods</h4>Adult patients with rheumatic diseases receiving prednisolone ≥0.6 mg/kg/day were randomized into the single-strength group (SS; SMX/TMP 400/80 mg daily), the half-strength group (HS; 200/40 mg daily) or the escalation group (ES; starting at 40/8 mg and increasing in ...[more]

PMID: 33134810

Similar Datasets

Project description:ObjectivesTo investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis.MethodsThis study included 28,292 treatment episodes with prolonged (??4?weeks), non-high-dose steroids (low dose [<?15?mg/day, n?=?27,227] and medium dose [??15 to <?30?mg/day, n?=?1065], based on prednisone) over a 14-year period. Risk factors for PCP and prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) were investigated if the 1-year incidence rate (IR) of PCP in each dose group was >?0.1/100 person-years. Cox regression with LASSO was used for analysis.ResultsOne-year PCP IR in the low-dose group was 0.01 (95% CI 0.001-0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2-1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n?=?173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1-8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR?=?0.2 (0.001-2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3-71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17-226)) was lower than the number needed to harm by serious ADR (45 (15-?)).ConclusionIncidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.

Project description:BACKGROUND:The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. METHODS:This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. RESULTS:Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (<?10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications. CONCLUSION:AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709.

Project description:BackgroundThe current study evaluated the long-term (52 week) safety and impact on symptom measures of lurasidone (with or without lithium or valproate) for the treatment of bipolar I disorder in Japanese patients.MethodsBipolar patients for this open-label flexibly dosed lurasidone (20-120 mg/day) study were recruited from those with a recent/current depressive episode who completed an initial 6 week, double-blind, placebo-controlled, lurasidone study (depressed group), and those with a recent/current manic, hypomanic, or mixed episode (non-depressed group) who agreed to enroll directly into the long-term study. Measures of adverse events and safety included treatment-emergent adverse events, vital signs, body weight, ECG, laboratory tests, and measures of suicidality and extrapyramidal symptoms. Symptom measures included Montgomery Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS).ResultsThe most common adverse events associated with lurasidone were akathisia (30.7%), nasopharyngitis (26.6%), nausea (12.1%), and somnolence (12.1%). Minimal changes in lipids and measures of glycemic control occurred. Mean change in body weight was + 1.0 kg in the non-depressed group and - 0.8 kg in the depressed group. MADRS total scores declined by a mean (SD) of 2.0 (14.7) points from long-term baseline to endpoint in the depressed group who had received placebo in the prior 6 week trial. The depressed group that had received lurasidone during the prior 6 week study maintained their depressive symptom improvements. For the non-depressed group, YMRS total scores decreased over time.LimitationsNo control group was included, treatment was open-label, and 49.7% of patients completed the 52 week study.ConclusionsLong-term treatment with lurasidone 20-120 mg/day for Japanese patients with bipolar disorder maintained improvements in depressive symptoms for depressed patients who were treated in a prior 6 week trial and led to improvements in manic symptoms among a newly recruited subgroup of patients with a recent/current manic, hypomanic, or mixed episode. Few changes in weight or metabolic parameters were evident.Clinical trial registrationJapicCTI-132319, clinicaltrials.gov-NCT01986114.

Project description:The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.

Project description:Background:We have reported previously the insufficient absolute number or functional defects of regulatory T cells (Tregs) in patients with rheumatoid arthritis (RA), challenging conventional unspecific immunosuppressive therapy. Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs; here, we investigated the efficacy of low-dose sirolimus combined with conventional immunosuppressants (sirolimus immunoregulation therapy) for RA treatment with lower side effects and better tolerance. Methods:In this nonblinded and parallel-group trial, we randomly assigned 62 patients to receive conventional glucocorticoids and immunosuppressants with or without sirolimus at a dosage of 0.5 mg on alternate days for 24 weeks in a 2 : 1 ratio. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups and CD4+T subsets were compared before and after the treatment. Results:Finally, 37 patients in the sirolimus group and 18 in the conventional treated group completed the 6-month study. By 24 weeks, the patients with sirolimus experienced significant reduction in disease activity indicators including DAS28, ESR, and the number of tender joints and swollen joints (p < 0.001). Notably, they had a higher level of Tregs as compared with those with conventional therapy alone (p < 0.05), indicating that sirolimus could partly restore the reduced Tregs. Concomitantly, their usage of immunosuppressants for controlling disease activity was decreased as compared with the conventional group with no difference in blood routine, and liver and renal functions both before and after the treatment of sirolimus and between the two groups (p > 0.05). Conclusions:Low-dose sirolimus immunoregulatory therapy selectively upregulated Tregs and partly replaced the usage of immunosuppressants to control disease activity without overtreatment and evaluable side effect. Further study is required using a large sample of RA patients treated with sirolimus for a longer period. This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=17245).

Dataset Information

An open-label, randomized controlled trial of sulfamethoxazole-trimethoprim for Pneumocystis prophylaxis: results of 52-week follow-up.

Publications

An open-label, randomized controlled trial of sulfamethoxazole-trimethoprim for <i>Pneumocystis</i> prophylaxis: results of 52-week follow-up.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure