Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Can families help veterans get more from PTSD treatment? A randomized clinical trial examining Prolonged Exposure with and without family involvement

Abstract Background Posttraumatic stress disorder occurs in as many as one in five combat veterans and is associated with a host of negative, long-term consequences to the individual, their families, and society at large. Trauma-focused treatments, such as Prolonged Exposure, result in clinically significant symptom relief for many. Adherence to these treatments (i.e., session attendance and homework compliance) is vital to ensuring recovery but can be challenging for patients. Engaging families in veterans’ treatment could prove to be an effective strategy for promoting treatment adherence while also addressing long-standing calls for better family inclusion in treatment for posttraumatic stress disorder. This paper describes the methods of a pragmatic randomized controlled trial designed to evaluate if family inclusion in Prolonged Exposure can improve treatment adherence. Methods One hundred fifty-six veterans, with clinically significant symptoms of posttraumatic stress disorder, will be randomized to receive either standard Prolonged Exposure or Prolonged Exposure enhanced through family inclusion (Family-Supported Prolonged Exposure) across three different VA facilities. Our primary outcomes are session attendance and homework compliance. Secondary outcomes include posttraumatic stress disorder symptom severity, depression, quality of life, and relationship functioning. The study includes a concurrent process evaluation to identify potential implementation facilitators and barriers to family involvement in Prolonged Exposure within VA. Discussion While the importance of family involvement in posttraumatic stress disorder treatment is non-controversial, there is no evidence base supporting best practices on how to integrate families into PE or any other individually focused trauma-focused treatments for posttraumatic stress disorder. This study is an important step in addressing this gap, contributing to the literature for both retention and family involvement in trauma-focused treatments. Trial registration ClinicalTrials.gov NCT03256227 . Registered on August 21, 2017.http://deepblue.lib.umich.edu/bitstream/2027.42/173826/1/13063_2022_Article_6183.pd

Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among US Veterans

ImportancePosttraumatic stress disorder (PTSD) is a prevalent and serious mental health problem. Although there are effective psychotherapies for PTSD, there is little information about their comparative effectiveness.ObjectiveTo compare the effectiveness of prolonged exposure (PE) vs cognitive processing therapy (CPT) for treating PTSD in veterans.Design, setting, and participantsThis randomized clinical trial assessed the comparative effectiveness of PE vs CPT among veterans with military-related PTSD recruited from outpatient mental health clinics at 17 Department of Veterans Affairs medical centers across the US from October 31, 2014, to February 1, 2018, with follow-up through February 1, 2019. The primary outcome was assessed using centralized masking. Tested hypotheses were prespecified before trial initiation. Data were analyzed from October 5, 2020, to May 5, 2021.InterventionsParticipants were randomized to 1 of 2 individual cognitive-behavioral therapies, PE or CPT, delivered according to a flexible protocol of 10 to 14 sessions.Main outcomes and measuresThe primary outcome was change in PTSD symptom severity on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from before treatment to the mean after treatment across posttreatment and 3- and 6-month follow-ups. Secondary outcomes included other symptoms, functioning, and quality of life.ResultsAnalyses were based on all 916 randomized participants (730 [79.7%] men and 186 [20.3%] women; mean [range] age 45.2 [21-80] years), with 455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95% CI, 39.1-40.7] points) and 461 participants randomized to CPT (mean CAPS-5 score at baseline, 40.3 [95% CI, 39.5-41.1] points). PTSD severity on the CAPS-5 improved substantially in both PE (standardized mean difference [SMD], 0.99 [95% CI, 0.89-1.08]) and CPT (SMD, 0.71 [95% CI, 0.61-0.80]) groups from before to after treatment. Mean improvement was greater in PE than CPT (least square mean, 2.42 [95% CI, 0.53-4.31]; P = .01), but the difference was not clinically significant (SMD, 0.17). Results for self-reported PTSD symptoms were comparable with CAPS-5 findings. The PE group had higher odds of response (odds ratio [OR], 1.32 [95% CI, 1.00-1.65]; P < .001), loss of diagnosis (OR, 1.43 [95% CI, 1.12-1.74]; P < .001), and remission (OR, 1.62 [95% CI, 1.24-2.00]; P < .001) compared with the CPT group. Groups did not differ on other outcomes. Treatment dropout was higher in PE (254 participants [55.8%]) than in CPT (215 participants [46.6%]; P < .01). Three participants in the PE group and 1 participant in the CPT group were withdrawn from treatment, and 3 participants in each treatment dropped out owing to serious adverse events.Conclusions and relevanceThis randomized clinical trial found that although PE was statistically more effective than CPT, the difference was not clinically significant, and improvements in PTSD were meaningful in both treatment groups. These findings highlight the importance of shared decision-making to help patients understand the evidence and select their preferred treatment.Trial registrationClinicalTrials.gov Identifier: NCT01928732

Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among US Veterans: A Randomized Clinical Trial

Importance: Posttraumatic stress disorder (PTSD) is a prevalent and serious mental health problem. Although there are effective psychotherapies for PTSD, there is little information about their comparative effectiveness. Objective: To compare the effectiveness of prolonged exposure (PE) vs cognitive processing therapy (CPT) for treating PTSD in veterans. Design, Setting, and Participants: This randomized clinical trial assessed the comparative effectiveness of PE vs CPT among veterans with military-related PTSD recruited from outpatient mental health clinics at 17 Department of Veterans Affairs medical centers across the US from October 31, 2014, to February 1, 2018, with follow-up through February 1, 2019. The primary outcome was assessed using centralized masking. Tested hypotheses were prespecified before trial initiation. Data were analyzed from October 5, 2020, to May 5, 2021. Interventions: Participants were randomized to 1 of 2 individual cognitive-behavioral therapies, PE or CPT, delivered according to a flexible protocol of 10 to 14 sessions. Main Outcomes and Measures: The primary outcome was change in PTSD symptom severity on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from before treatment to the mean after treatment across posttreatment and 3- and 6-month follow-ups. Secondary outcomes included other symptoms, functioning, and quality of life. Results: Analyses were based on all 916 randomized participants (730 [79.7%] men and 186 [20.3%] women; mean [range] age 45.2 [21-80] years), with 455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95% CI, 39.1-40.7] points) and 461 participants randomized to CPT (mean CAPS-5 score at baseline, 40.3 [95% CI, 39.5-41.1] points). PTSD severity on the CAPS-5 improved substantially in both PE (standardized mean difference [SMD], 0.99 [95% CI, 0.89-1.08]) and CPT (SMD, 0.71 [95% CI, 0.61-0.80]) groups from before to after treatment. Mean improvement was greater in PE than CPT (least square mean, 2.42 [95% CI, 0.53-4.31]; P = .01), but the difference was not clinically significant (SMD, 0.17). Results for self-reported PTSD symptoms were comparable with CAPS-5 findings. The PE group had higher odds of response (odds ratio [OR], 1.32 [95% CI, 1.00-1.65]; P \u3c .001), loss of diagnosis (OR, 1.43 [95% CI, 1.12-1.74]; P \u3c .001), and remission (OR, 1.62 [95% CI, 1.24-2.00]; P \u3c .001) compared with the CPT group. Groups did not differ on other outcomes. Treatment dropout was higher in PE (254 participants [55.8%]) than in CPT (215 participants [46.6%]; P \u3c .01). Three participants in the PE group and 1 participant in the CPT group were withdrawn from treatment, and 3 participants in each treatment dropped out owing to serious adverse events. Conclusions and Relevance: This randomized clinical trial found that although PE was statistically more effective than CPT, the difference was not clinically significant, and improvements in PTSD were meaningful in both treatment groups. These findings highlight the importance of shared decision-making to help patients understand the evidence and select their preferred treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01928732