Convalescent plasma for COVID-19 in hospitalised patients: an open-label, randomised clinical trial.

BACKGROUND: The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients. METHODS: This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment. RESULTS: A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48-68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8-12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference -3.7%, 95% CI -18.8-11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups. CONCLUSIONS: CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone.

Early antiretroviral therapy for HIV-infected patients admitted to an intensive care unit (EARTH-ICU): A randomized clinical trial.

BACKGROUND: Highly active antiretroviral therapy (HAART) has reduced HIV-related morbidity and mortality at all stages of infection and reduced transmission of HIV. Currently, the immediate start of HAART is recommended for all HIV patients, regardless of the CD4 count. There are several concerns, however, about starting treatment in critically ill patients. Unpredictable absorption of medication by the gastrointestinal tract, drug toxicity, drug interactions, limited reserve to tolerate the dysfunction of other organs resulting from hypersensitivity to drugs or immune reconstitution syndrome, and the possibility that subtherapeutic levels of drug may lead to viral resistance are the main concerns. The objective of our study was to compare the early onset (up to 5 days) with late onset (after discharge from the ICU) of HAART in HIV-infected patients admitted to the ICU. METHODS: This was a randomized, open-label clinical trial enrolling HIV-infected patients admitted to the ICU of a public hospital in southern Brazil. Patients randomized to the intervention group had to start treatment with HAART within 5 days of ICU admission. For patients in the control group, treatment should begin after discharge from the ICU. The patients were followed up to determine mortality in the ICU, in the hospital and at 6 months. The primary outcome was hospital mortality. The secondary outcome was mortality at 6 months. RESULTS: The calculated sample size was 344 patients. Unfortunately, we decided to discontinue the study due to a progressively slower recruitment rate. A total of 115 patients were randomized. The majority of admissions were for AIDS-defining illnesses and low CD4. The main cause of admission was respiratory failure. Regarding the early and late study groups, there was no difference in hospital (66.7% and 63.8%, p = 0.75) or 6-month (68.4% and 79.2%, p = 0.20) mortality. After multivariate analysis, the only independent predictors of in-hospital mortality were shock and dialysis during the ICU stay. For the mortality outcome at 6 months, the independent variables were shock and dialysis during the ICU stay and tuberculosis at ICU admission. CONCLUSIONS: Although the early termination of the study precludes definitive conclusions being made, early HAART administration for HIV-infected patients admitted to the ICU compared to late administration did not show benefit in hospital mortality or 6-month mortality. ClinicalTrials.gov, NCT01455688. Registered 20 October 2011, https://clinicaltrials.gov/show/NCT01455688.

Renal Outcomes of Vasopressin and Its Analogs in Distributive Shock: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVES: To systematically review the literature and synthesize evidence concerning the effects of vasopressin and its analogs compared with other vasopressors in distributive shock, focusing on renal outcomes. DATA SOURCES: We performed a systematic review in MEDLINE, Embase, Cochrane Central, and Clinicaltrials.gov databases. STUDY SELECTION: Randomized clinical trials that compared vasopressin and its analogs with other vasopressors and reported renal outcomes in adult patients with distributive shock. DATA EXTRACTION: Paired reviewers independently screened citations, conducted data extraction and assessed risk of bias. Three prespecified subgroup analyses were conducted. Three main outcomes related to acute renal failure were analyzed: the need for renal replacement therapy, acute kidney injury incidence, and acute kidney injury-free days. I test was used to evaluate heterogeneity between studies. Substantial heterogeneity was defined as I greater than 50%. A random-effects model with Mantel-Haenszel weighting was used for all analyses. Heterogeneity was explored using subgroup analysis. The quality of evidence for intervention effects was summarized using Grading of Recommendations Assessment, Development, and Evaluation methodology. This study was registered in the PROSPERO database (CRD42017054324). DATA SYNTHESIS: Three-thousand twenty-six potentially relevant studies were identified, and 30 articles were reviewed in full. Seventeen studies met the inclusion criteria, including a total of 2,833 individuals. Of these, 11 studies (2,691 individuals) were suitable for quantitative meta-analysis. Overall, the evidence was of low to moderate quality. Patients who received vasopressin and its analogs had a reduced need for renal replacement therapy (odds ratio, 0.59 [0.37-0.92]; p = 0.02; I = 49%) and a lower acute kidney injury incidence (odds ratio, 0.58 [0.37-0.92]; p = 0.02; I = 63%). These results should be interpreted with caution, due to excessive heterogeneity. Acute kidney injury-free data was not pooled, since the small number of studies and extreme heterogeneity. CONCLUSIONS: In patients with distributive shock, vasopressin and its analogs use is associated with a reduced need for renal replacement therapy and lower acute kidney injury incidence. These results are supported by high risk of bias evidence.

Spontaneous Breathing Trials With T-Piece or Pressure Support Ventilation.

Spontaneous breathing trials (SBTs) are among the most commonly employed techniques to facilitate weaning from mechanical ventilation. The preferred SBT technique, however, is still unclear. To clarify the preferable SBT (T-piece or pressure support ventilation [PSV]), we conducted this systematic review. We then searched the MEDLINE, EMBASE, SciELO, Google Scholar, CINAHL, ClinicalTrials.gov, and Cochrane CENTRAL databases through June 2015, without language restrictions. We included randomized controlled trials involving adult subjects being weaned from mechanical ventilation comparing T-piece with PSV and reporting (1) weaning failure, (2) re-intubation rate, (3) ICU mortality, or (4) weaning duration. Anticipating clinical heterogeneity among the included studies, we compared prespecified subgroups: (1) simple, difficult, or prolonged weaning and (2) subjects with COPD. We summarized the quality of evidence for intervention effects using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. We identified 3,674 potentially relevant studies and reviewed 23 papers in full. Twelve studies (2,161 subjects) met our inclusion criteria. Overall, the evidence was of very low to low quality. SBT technique did not influence weaning success (risk ratio 1.23 [0.94-1.61]), ICU mortality (risk ratio 1.11 [0.80-1.54]), or re-intubation rate (risk ratio 1.21 [0.90-1.63]). Prespecified subgroup analysis suggested that PSV might be superior to T-piece with regard to weaning success for simple-to-wean subjects (risk ratio 1.44 [1.11-1.86]). For the prolonged-weaning subgroup, however, T-piece was associated with a shorter weaning duration (weighted mean difference -3.08 [-5.24 to -0.92] d). In conclusion, low-quality evidence is available concerning this topic. PSV may be associated with lower weaning failure rates in the simple-to-wean subgroup. In contrast, in prolonged-weaning subjects, T-piece may be related to a shorter weaning duration, although this is at high risk of bias. Further study of the difficult-to-wean and COPD subgroups is required.