Dataset Information

Timing of antiretroviral therapy for HIV-infected patients with moderate to severe Pneumocystis pneumonia: study protocol for a multi-centre prospective randomised controlled trial.

ABSTRACT:

Background

Pneumocystis pneumonia (PCP) is a common acquired immune deficiency syndrome (AIDS)-related opportunistic infection. Recent reports estimate that more than 400,000 patients with human immunodeficiency virus (HIV) develop PCP each year globally. However, the timing of antiretroviral therapy (ART) initiation for HIV-infected patients with PCP is still controversial, and the benefits and risks of early initiation of ART are not completely clear. We thus designed this study in order to determine the optimal timing for ART initiation for HIV-positive patients with moderate to severe PCP.

Methods

This study will be an open-label, multi-centre, prospective randomised controlled trial. A total of 200 subjects will be randomly assigned to an early ART initiation group (?14?days after PCP diagnosis) and a deferred ART initiation group (>14?days after PCP diagnosis) at a 1:1 ratio. All subjects will be followed up for 48?weeks after starting ART. The primary endpoint is incidence of disease progression (including new or relapsing opportunistic infections and death) at week 48. The secondary endpoints are the changes in CD4 counts from baseline at weeks 12, 24 and 48; the degree of virological suppression (HIV RNA?DiscussionWe hope that the results of this study will reveal the optimal timing for initiation of ART in HIV-infected patients with moderate to severe PCP.

Trial registration

This trial was registered as one of the 12 trials under the name of a general project at chictr.org.cn on February 1, 2019. The registration number of the general project is ChiCTR1900021195.

SUBMITTER: Qin Y

PROVIDER: S-EPMC7310256 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Timing of antiretroviral therapy for HIV-infected patients with moderate to severe Pneumocystis pneumonia: study protocol for a multi-centre prospective randomised controlled trial.

Qin Yuanyuan Y Lu Yanqiu Y Zhou Yihong Y Harypursat Vijay V Sun Feng F Yang Sen S Tang Shengquan S Li Yao Y He Xiaoqing X Zeng Yanming Y Chen Yaokai Y

Trials 20200622 1

<h4>Background</h4>Pneumocystis pneumonia (PCP) is a common acquired immune deficiency syndrome (AIDS)-related opportunistic infection. Recent reports estimate that more than 400,000 patients with human immunodeficiency virus (HIV) develop PCP each year globally. However, the timing of antiretroviral therapy (ART) initiation for HIV-infected patients with PCP is still controversial, and the benefits and risks of early initiation of ART are not completely clear. We thus designed this study in ord ...[more]

PMID: 32571429

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Project description:BackgroundNafamostat, a serine protease inhibitor, has been used for the treatment of disseminated intravascular coagulation and pancreatitis. In vitro studies and clinical reports suggest its beneficial effect in the treatment of COVID-19 pneumonia.MethodsThis phase 2 open-label, randomised, multicentre, controlled trial evaluated nafamostat (4.8 mg/kg/day) plus standard-of-care (SOC) in hospitalised patients with COVID-19 pneumonia (i.e., those requiring nasal high-flow oxygen therapy and/or non-invasive mechanical ventilation). The primary outcome was the time to clinical improvement. Key secondary outcomes included the time to recovery, rates of recovery and National Early Warning Score (NEWS). The trial is registered with ClinicalTrials.gov Identifier: NCT04623021.FindingsA total of 104 patients, mean age 58.6 years were enrolled in 13 clinical centres in Russia between 25/9/2020 and 14/11/2020 and randomised to nafamostat plus SOC (n=53) or SOC alone (n=51). There was no significant difference in time to clinical improvement (primary endpoint) between the nafamostat and SOC groups (median 11 [interquartile range (IQR) 9 to 14) vs 11 [IQR 9 to 14] days; Rate Ratio [RR; the ratio for clinical improvement], 1.00; 95% CI, 0.65 to 1.57; p=0.953). In 36 patients with baseline NEWS ≥7, nafamostat was superior to SOC alone in median time to clinical improvement (11 vs 14 days; RR, 2.89; 95% CI, 1.17 to 7.14; p=0.012). Patients receiving nafamostat in this subgroup had a significantly higher recovery rate compared with SOC alone (61.1% (11/18) vs 11.1 % (2/18) by Day 11, p=0.002). The 28-day mortality was 1.9% (1/52) for nafamostat and 8.0% (4/50) for SOC (95% CI, -17.0 to 3.4; p=0.155). No case of COVID-19 related serious adverse events leading to death was recorded in the patients receiving nafamostat.InterpretationOur study found no significant difference in time to clinical improvement between the nafamostat and SOC groups, but a shorter median time to clinical improvement in a small group of high-risk COVID-19 patients requiring oxygen treatment. To assess the efficacy further, a larger Phase 3 clinical trial is warranted.FundingKorea Research Institute of Bioscience and Biotechnology [2020M3A9H5108928] and Chong Kun Dang (CKD) Pharm (Seoul, Korea).

Project description:ImportanceConsidering the lack of equipoise regarding the timing of cholecystectomy in patients with moderately severe and severe acute biliary pancreatitis (ABP), it is critical to assess this issue.ObjectiveTo assess the outcomes of early cholecystectomy (EC) in patients with moderately severe and severe ABP.Design, settings, and participantsThis cohort study retrospectively analyzed real-life data from the MANCTRA-1 (Compliance With Evidence-Based Clinical Guidelines in the Management of Acute Biliary Pancreatitis) data set, assessing 5304 consecutive patients hospitalized between January 1, 2019, and December 31, 2020, for ABP from 42 countries. A total of 3696 patients who were hospitalized for ABP and underwent cholecystectomy were included in the analysis; of these, 1202 underwent EC, defined as a cholecystectomy performed within 14 days of admission. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality and morbidity. Data analysis was performed from January to February 2023.Main outcomesMortality and morbidity after EC.ResultsOf the 3696 patients (mean [SD] age, 58.5 [17.8] years; 1907 [51.5%] female) included in the analysis, 1202 (32.5%) underwent EC and 2494 (67.5%) underwent delayed cholecystectomy (DC). Overall, EC presented an increased risk of postoperative mortality (1.4% vs 0.1%, P < .001) and morbidity (7.7% vs 3.7%, P < .001) compared with DC. On the multivariable analysis, moderately severe and severe ABP were associated with increased mortality (odds ratio [OR], 361.46; 95% CI, 2.28-57 212.31; P = .02) and morbidity (OR, 2.64; 95% CI, 1.35-5.19; P = .005). In patients with moderately severe and severe ABP (n = 108), EC was associated with an increased risk of mortality (16 [15.6%] vs 0 [0%], P < .001), morbidity (30 [30.3%] vs 57 [5.5%], P < .001), bile leakage (2 [2.4%] vs 4 [0.4%], P = .02), and infections (12 [14.6%] vs 4 [0.4%], P < .001) compared with patients with mild ABP who underwent EC. In patients with moderately severe and severe ABP (n = 108), EC was associated with higher mortality (16 [15.6%] vs 2 [1.2%], P < .001), morbidity (30 [30.3%] vs 17 [10.3%], P < .001), and infections (12 [14.6%] vs 2 [1.3%], P < .001) compared with patients with moderately severe and severe ABP who underwent DC. On the multivariable analysis, the patient's age (OR, 1.12; 95% CI, 1.02-1.36; P = .03) and American Society of Anesthesiologists score (OR, 5.91; 95% CI, 1.06-32.78; P = .04) were associated with mortality; severe complications of ABP were associated with increased mortality (OR, 50.04; 95% CI, 2.37-1058.01; P = .01) and morbidity (OR, 33.64; 95% CI, 3.19-354.73; P = .003).Conclusions and relevanceThis cohort study's findings suggest that EC should be considered carefully in patients with moderately severe and severe ABP, as it was associated with increased postoperative mortality and morbidity. However, older and more fragile patients manifesting severe complications related to ABP should most likely not be considered for EC.

Project description:IntroductionPneumocystis pneumonia is a common opportunistic infection in patients with HIV/AIDS, and is a leading cause of death in this population. Early selection of effective treatment is therefore critical to reduce mortality. We conducted a clinical trial to compare the effectiveness and safety of three different antifungal treatment regimens in HIV-infected patients with moderate to severe PCP.MethodsOur study was a multicenter, observational prospective clinical trial. We recruited 320 HIV-infected patients with moderate to severe PCP, and stratified these subjects into a trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy group, a TMP-SMX plus clindamycin group, and a TMP-SMX plus caspofungin group. Patients were invited to participate in 12 weeks of follow-up. Outcomes included the difference in overall mortality and the proportion of overall positive response to treatment in the three groups at weeks 4 and 12, the difference in treatment duration, and the proportion of adverse events among the three groups during the study period.ResultsThe probability of survival not statistically different among three treatment groups. Mortality in the TMP-SMX monotherapy group (group 1) was 15/115 (13.04%) vs. 20/83 (24.10%) in the TMP-SMX plus clindamycin group (group 2) vs. 24/107 (22.43%) in the TMP-SMX plus caspofungin group (group 3) at week 12 (p = 0.092). The overall positive response rate to treatment in the three groups was 24.14%, 34.94%, and 38.32%, respectively, at week 4, and 33.91%, 38.55%, and 44.86%, respectively, at week 12. No significant difference in the overall positive response rate to treatment at either week 4 or week 12 was noted (p = 0.061, p = 0.246). Rates of changes to therapy were 6.50% (8/123) in group 1, 3.40% (3/87) in group 2, and 2.70% (3/110) in group 3, and did not differ significantly among the three groups (p = 0.376). There were also no significant differences in adverse events among the three treatment groups of patients with moderate to severe PCP.ConclusionsOur results indicate that there are no significant statistical differences among the three studied treatment regimens in terms of antifungal effectiveness in HIV-infected patients with moderate to severe PCP. TMP-SMX monotherapy is a convenient, cheap, and effective therapeutic drug regimen to treat HIV-infected patients with moderate to severe PCP, and is an appropriate treatment strategy in resource-limited settings.Clinical trial registrationwww.ClinicalTrials.gov , ID: ChiCTR1900021195. Registered on February 1, 2019.

Dataset Information

Timing of antiretroviral therapy for HIV-infected patients with moderate to severe Pneumocystis pneumonia: study protocol for a multi-centre prospective randomised controlled trial.

Background

Methods

Trial registration

Publications

Timing of antiretroviral therapy for HIV-infected patients with moderate to severe Pneumocystis pneumonia: study protocol for a multi-centre prospective randomised controlled trial.

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