Trials Network Research Articles

Participant acceptability and clinician satisfaction of cognitive behavioural therapy and medication management algorithm compared with enhanced standard care for treatment of depression among youth with HIV

Background: Primary results of the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) 2002 trial showed that cognitive behavioural therapy (CBT) and medication management algorithm (MMA) (COMB-R) significantly improved depression in youth with HIV (YWH) compared with enhanced standard care (ESC). Acceptability and satisfaction were examined among study participants and clinicians. Method: Between March 2017 and March 2019, 13 U.S. sites enrolled YWH, aged 12–24, diagnosed with nonpsychotic depression. Sites were randomised to either COMB-R (CBT by a therapist and licensed prescriber) or ESC (standard psychotherapy and medication management). After the intervention (week 24), participants, prescribers, and therapists rated acceptability and satisfaction. We compared site-level means using Wilcoxon tests. Results: Both COMB-R (n = 69) and ESC (n = 71) participants had a mean age of 21.4 years, with 53% female, and 54% having acquired HIV perinatally. Baseline age, sex, depression levels, RNA viral load, and CD4 count were comparable between arms. The distribution of site-level mean participant acceptability was greater in COMB-R compared with ESC (p = 0.04). The distribution of site-level mean prescriber satisfaction was greater in COMB-R (p = 0.01). The was no evidence that the site-level mean therapist satisfaction did not differ between arms (p = 0.52). Discussion: Acceptability and satisfaction for participants and licensed prescribers were higher at COMB-R sites compared with standard of care, indicating that this tailored, manual-guided, collaborative, measured care intervention was less burdensome in terms of the number of visits. Patient and medication provider satisfaction rates were higher than standard of care. Conclusion: While these results support the use of CBT and MMA in treating depression among YWH, further research is required to determine generalisability.

Abstract 4138252: Association between Pressure-Adjusted Heart Rate and Mortality in Cardiogenic Shock

Introduction: Among patients with cardiogenic shock (CS), high right atrial pressure (RAP) and low mean arterial pressure (MAP) are associated with in-hospital mortality. Pressure-adjusted heart rate (PAHR), defined as heart rate * RAP-to-MAP ratio (HR * [RAP/MAP]), integrates these parameters and has been used to identify cardiovascular dysfunction in critical illness. Higher PAHR values associate with higher surgical ICU mortality, but the prognostic significance of PAHR has not been assessed in cardiac intensive care unit (CICU) patients with CS. Hypothesis: We hypothesized that higher PAHR values are associated with higher risk of in-hospital mortality in patients with CS. Methods: The Critical Care Cardiology Trials Network (CCCTN) is a multinational registry of CICUs coordinated by the TIMI Study Group. Among CS admissions (2018-2023) undergoing invasive hemodynamic assessment within 24h of CICU admission, we calculated PAHR (in bpm) and assessed its relationship with in-hospital mortality. Patients on temporary mechanical circulatory support were excluded. Odds ratios were adjusted for age, sex, vasoactive-inotropic score (VIS), SCAI stage, and preceding cardiac arrest. Subgroup analyses stratifying by CS subtype were performed. Results: Among the 1411 CS admissions in the analysis cohort (mean age 61 years, 31% women), 18% had AMI-CS, 75% had HF-CS, and 7% had secondary CS. At the time of assessment (median 1.4h after CICU admission), 75% were on vasoactive support (median VIS 3.8). Median HR was 92 (Q1-Q3 77-109) bpm, RAP 15 (Q1-Q3 10-19) mmHg, MAP 75 (Q1-Q3 67-87) mmHg, and PAHR 17 (Q1-Q3 11-24) bpm. A stepwise gradient of higher in-hospital mortality with increasing PAHR values (p-trend <0.001; Fig ) was observed. In adjusted models, a higher PAHR was associated with higher in-hospital mortality (aOR per 10-bpm, 1.35 [95% CI, 1.15-1.58]), and had stronger prognostic associations with mortality than its individual hemodynamic components (Fig) . Conclusion: Higher PAHR is strongly associated with in-hospital mortality in CS patients. PAHR, a simple parameter which is readily calculable without needing a pulmonary artery catheter, may aid in identifying CS patients at higher risk of death.

School environment and adolescent health: Results from the HPTN 068 cohort

PurposeTo assess the relationship between school environment and health and behavior outcomes. MethodsData are from baseline and first follow-up of the HIV Prevention Trials Network (HPTN) 068 longitudinal trial established in 2012 of adolescent girls and young women in rural Mpumalanga Province, South Africa. Data from 2212 participants are included. We measured the association between four school environment domains: school resources, school safety, negative personal experiences, and school connectedness, and several health and behavior outcomes: depressive symptoms, low attendance, recent pregnancy, recent unprotected sex, transactional sex, and having an older romantic partner. We used a g-computation approach to estimate risk differences (RD) for the longitudinal relationship between the school environment (measured at the individual and school level) on individual health and behavior outcomes, controlling for baseline covariates. ResultsThe mean age of participants at baseline was 15.4; mean age at first follow-up was 16.6. Individual baseline perceptions of an unsafe school environment (RD = 3.1 %, 95 % CI: 1.3–5.2 %) and more frequent negative experiences (RD = 4.0 %, 95 % CI: 2.0–5.9 %) were associated with higher absolute risk of depressive symptoms at follow-up. There was an overall trend toward higher risk of pregnancy, unprotected sex, and having an older partner among those who reported fewer school resources, lack of school safety, more negative personal experiences, and lack of school connectedness. ConclusionsOur findings provide evidence of an overall trend toward higher risk of depression, pregnancy, unprotected sex, and having an older partner among those reporting a worse school environment across four school environment domains.

Young patients in the cardiac intensive care unit: insights from the critical care cardiology trials network registry

Abstract Background Elderly patients treated in the cardiac intensive care unit (CICU) have engendered much warranted investigation. However, little is known about young patients as another distinct population. Purpose: To describe the demographics, clinical profiles, and outcomes of young CICU patients in order to understand any distinct needs and challenges of this population. Methods: We analyzed consecutive admissions to adult CICUs from 2018 to 2023 in the Critical Care Cardiology Trials Network (CCCTN), a multicenter prospective registry of advanced CICUs in North America coordinated by the TIMI Study Group. Patients aged <40 years were classified as "young patients" and compared to patients ≥ 40 years of age. Results: Among 29,035 CICU admissions during the study period, the median age was 67 years (25th, 75th %iles: 56, 70). Admissions 18 to 40 years of age comprised 6.7% (n=1959) of total admissions. The young cohort was more likely to be female (40.0% vs 36.4%, p=0.0015) and non-Caucasian (55.3% vs. 43.0%, p<0.0001). Traditional cardiovascular risk factors were less common among the young, as were prior cardiovascular diagnoses other than congenital heart disease and pulmonary hypertension. Initial SOFA scores and serum lactate levels were similar in the 2 groups (Table). The most common CICU admission diagnoses in the young were heart failure (HF), arrhythmia, and acute coronary syndrome (ACS) (Panel A). Of these, HF was more common in the young (26.4% vs 19.5%, p<0.0001), while arrhythmia (16.8% vs 18.9%, p=0.03) and ACS (10.9% vs 29.4%, p<0.0001) were less common compared to the older group (Panel B). Tamponade, hypertensive emergency, and congenital disease were more common in the young (Panel B). Respiratory insufficiency was the most common indication for admission to CICU in the young (24.6%) followed by cardiogenic shock (22.4%), unstable arrythmia (15.7%), and cardiac arrest (12.7%, Panel C). Critical care resources, other than coronary angiography/PCI, were utilized significantly more often in the young group (Panel D). Overall utilization of mechanical circulatory support (MCS) was modestly higher among the young cohort (13.1% vs. 11.4%, p=0.03, Panel D); however, among those managed with MCS, the % of MCS that was ECMO was higher among the young (29.3% vs 9.9%, p<0.0001). Young admissions had longer CICU stays (2.7 [1.2-5.9] vs 2.3 [1.2-4.9], p<0.0001). CICU mortality (6.5% vs 10.5%, p<0.0001) and hospital mortality (9.5% vs 14.4%, p<0.0001) were significantly lower in the young. Conclusion: Patients under the age of 40 admitted to CICUs presented with similar disease severity to older patients but more often had shock or cardiac arrest, had longer ICU stays, and more use of advanced ICU therapies but with lower in-hospital mortality. This important patient cohort merits continued clinical and research focus.

Hoping to Adhere? Examining the Relationship Between Hope and Pre-exposure Prophylaxis Willingness, Adherence, and Persistence Among Young Women in South Africa and Zimbabwe (HPTN 082).

Hope is a powerful psychological construct which is linked to positive health. Greater hope is associated with improved antiretroviral therapy adherence; however, less is known about the impact of hope on oral pre-exposure prophylaxis (PrEP) outcomes. HIV Prevention Trials Network 082, was an open-label PrEP study among young women (ages 16-25) in South Africa and Zimbabwe. Hope was measured at baseline and follow-up using a subset of the Hope for the Future Scale (score range 6-24) and PrEP willingness was measured using a subscale of the HIV Prevention Readiness Measure (score range 6-30). Intracellular tenofovir-diphosphate (TFV-DP) concentrations were obtained from dried blood spot samples at weeks 13, 26, and 52; high PrEP adherence was defined as TFV-DP concentrations ≥ 700 fmol/punch. Persistence was defined as TFV-DP > 16 fmol/punch at weeks 26 and 52. Linear regression and generalized estimating equations were used to assess the relationship between hope and PrEP willingness, adherence, and persistence. The median age of participants (n = 432) was 21years (interquartile range [IQR]: 19-22). The mean hope score at baseline was 21.0 (SD = 3.4). Although hope was positively associated with PrEP willingness (β = 0.22, 95% CI 0.15, 0.37), it was not associated with high PrEP adherence (aRR = 1.00, 95% CI 0.96, 1.05), or persistence at follow-up (aRR = 1.02, 95% CI 0.99, 1.05). While cultivating hope may be an important strategy in building willingness to take oral PrEP, it may not be enough to sustain PrEP adherence or persistence.

Incremental eligibility criteria for the BMT CTN 1507 haploidentical trial for children with sickle cell disease

AbstractThe Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1507 leadership and the data safety monitoring board (DSMB) established incremental entry criteria for children aged 5 to 14.99 years with sickle cell disease (SCD) enrolling in a phase 2 trial of HLA-haploidentical hematopoietic stem cell transplantation. First, the enrollment was limited to overt stroke in the first 10 participants (stage 4). Subsequently, the DSMB reviewed the interim results and expanded the eligibility to include children with silent cerebral infarcts or abnormal transcranial Doppler velocities with magnetic resonance angiography–defined cerebral vasculopathy (stage 3). A third cohort was enrolled after the DSMB reviewed the clinical outcomes in these cumulative initial enrollments (n = 18) and additions were made to the entry criteria that included nonneurologic morbidities (stage 2). Added eligibility criteria included the following: (1) life-threatening acute chest syndrome requiring exchange transfusion; (2) right heart catheterization confirmed pulmonary hypertension; (3) persistent systemic hypertension despite maximum medical therapy; (4) acute pain despite maximum medical therapy in the absence of psychosocial factors and unmanaged asthma after adjudication; and (5) 2 major priapism episodes in 12 months or 3 in 24 months. Children with SCD who did not meet the criteria for stages 4, 3, and 2 were not eligible. To our knowledge, for the first time, we introduce a staged strategy for eligibility in a curative therapy trial for children with SCD concordant with 45 Code of Federal Regulations § 46.405(b). The research governance–mandated eligibility strategy used within the BMT CTN 1507 phase 2 study may apply to future pediatric SCD curative therapy trials. This trial was registered at www.ClinicalTrials.gov as #NCT032635590.

Prenatal Substance Exposure and Infant Discharge Placement: Results From the ACT NOW Study.

It is critical that researchers gather evidence of factors that identify infants at risk of out-of-home placement based on types of substance exposures and demographic characteristics. This study applied a validated medical record data extraction tool on data derived from a multi-site (N = 30) pediatric clinical trials network (ISPCTN) study of Neonatal Opioid Withdrawal (ACT NOW study). Participants included 1808 birthing parent-infant dyads with documented NOWS scoring or prenatal opioid exposure. Non-Hispanic White pregnant persons comprised the largest proportion of the sample (69.8%), followed by Non-Hispanic Black (11.6%), Non-Hispanic Multiracial and Other race (8.5%), and Hispanic (6.2%). Most notably, infant prenatal substance exposure across alcohol, cocaine, meth/amphetamine, and opioids, had the lowest possibility of discharging to parent(s). Additionally, latent class analysis identified distinct classes of substance use during pregnancy that were associated with different probabilities of discharging to parent(s). Specifically, less than half of infants (47%-49%) in the Poly-use and Meth/amphetamine classes were discharged to their parent(s). Severity of infant withdrawal symptoms influenced placement decisions within the Poly-use and Prescription Opioid classes. Findings can inform standard practices for increasing support for pregnant persons and substance-exposed infants including identification, subsequent referrals, communication with Child Protective Services, and plans of safe care.

Cancer Immunotherapy Trials Network 12: Pembrolizumab in HIV-Associated Kaposi Sarcoma.

Cancer Immunotherapy Trials Network 12 demonstrated safety of pembrolizumab in treating advanced cancer in people with HIV. Here, we report results of the Kaposi sarcoma (KS) cohort. In this multicenter phase I trial, we enrolled participants with HIV-associated KS on antiretroviral therapy with CD4+ ≥50 cells/μL and HIV plasma RNA <200 copies/mL. Pembrolizumab 200 mg intravenously was administered once every 3 weeks for up to 35 cycles. The primary end point was safety, and the secondary end point was KS response by modified AIDS Clinical Trials Group Criteria. Thirty-two cisgender men enrolled with baseline median CD4+ T-cell count of 274 cells/µL. All but nine participants had received previous systemic KS therapy. Participants received a median of 11 cycles of pembrolizumab (range, 1-35). Sixty-six percent had grade ≥1 treatment-emergent adverse events, including one death from polyclonal KS herpesvirus-related B-cell lymphoproliferation. Thirty-one percent had ≥one immune-mediated AEs (imAEs) with 25% requiring systemic steroids. In 29 participants with evaluable KS, the overall response rate (ORR) was 62.1% (95% CI, 42.3 to 79.3) and did not differ by CD4+ T-cell count. ORR in the eight participants with evaluable disease without previous KS therapy was 87.5% (95% CI, 47.3 to 99.7). Median duration of response (DOR) was not reached, and the Kaplan-Meier estimate of DOR of ≥12 months was 92.3% (95% CI, 56.6 to 98.8). Median progression-free survival was 28.2 months (95% CI, 4.2 to noncalculable). Pembrolizumab yielded a high rate of durable responses in HIV-associated KS. imAEs were successfully managed with standard guidelines.

Variation in Opioid Agonist Dosing in Clinical Trials by Race and Ethnicity

Racial and ethnic disparities in access to treatment and quality of treatment for opioid use disorder (OUD) have been identified in usual care settings. In contrast, disparities in treatment quality within clinical trials are relatively unexamined. To estimate racial and ethnic differences in the dose of opioid agonist treatment for OUD in the first 4 weeks of treatment in clinical trials. This cohort study performed analysis of the methadone and buprenorphine treatment arms of 3 trials conducted by the National Institute on Drug Abuse Clinical Trials Network between May 2006, and January 31, 2017, at multiple Clinical Trials Network sites across the US. Trial participants who were randomized to and initiated buprenorphine or methadone treatment and who identified as Hispanic, non-Hispanic Black, or non-Hispanic White were included in the present study. Data were analyzed from November 1, 2023, to August 5, 2024. Combined race and ethnicity as self-classified by the patient at trial enrollment. The maximum daily dose of buprenorphine or methadone received in each week for the first 4 weeks of treatment. The mean dose and the percentage of patients receiving a higher dose (buprenorphine ≥16 mg and methadone ≥60 mg) were compared across race and ethnicity groups. A total of 1748 patients (1263 who initiated buprenorphine and 485 who initiated methadone treatment) were included in the analysis (1168 [66.8%] male; median age, 33 [IQR, 26-45] years). Of these, 138 patients (7.9%) identified as Black, 273 (15.6%) as Hispanic, and 1337 (76.5%) as White. In week 4, Black patients received buprenorphine doses 2.5 (95% CI -4.6 to -0.5) mg lower and methadone doses 16.7 (95% CI, -30.7 to -2.7) mg lower compared with White patients, after standardizing by age and sex. In week 4, the percentage of patients receiving a higher dose of medication (buprenorphine ≥16 mg; methadone ≥60 mg) was 16.9 (95% CI, -31.9 to -1.9) points lower for Black patients compared with White patients. Hispanic and White patients received similar buprenorphine doses; Hispanic patients received lower methadone doses than White patients. In this cohort study of data from 3 clinical trials, White patients generally received higher doses of medication than Black patients. Future research is needed to understand the mechanisms of and interventions to reduce disparities in OUD treatment quality and how such disparities impact generalizability of trial results.

Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial.

Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.

Quality of Caregiver-Adolescent Relationship on HIV, Herpes Simplex Virus Type-2, and on Pregnancy Among Young Women in South Africa Enrolled in HIV Prevention Trials Network 068

PurposeAdolescent girls and young women (AGYW) are at an increased risk of acquiring HIV and HSV-2, and unintended pregnancies are high in AGYW. Despite the protective impact of caregiver-adolescent relationships on risk behaviors, less attention has been paid to the association of these relationships and sexually transmitted infections (STIs) and pregnancy. MethodsWe used longitudinal data from HIV Prevention Trial Network 068, which was conducted among 2,533 AGYW (13 – 20 years) over 5 years in Agincourt, South Africa. Kaplan-Meier and Cox models were used to estimate the effect of quality of caregiver-adolescent relationships (caring and closeness) on STIs and pregnancy. Also, we assessed effect measure modification by age (14–19 vs. 20–25 years) for STI risk using stratum-specific estimates and likelihood ratio tests, with a p value <.1 indicative of effect measure modification. ResultsThere were no significant differences in the hazard of HIV by our exposures (caring: hazard ratio (HR): 1.03, 95% CI: 0.75, 1.42; closeness: HR: 0.80, 95% CI: 0.57, 1.11). Among 14–19-year-olds, those who reported caregiver caring were less likely to acquire HSV-2 (HR: 0.69, 95% CI: 0.51, 0.94, likelihood ratio tests= 3.89, p-value = .0487), in contrast, there were no significant differences among 20 – 25-year-olds. AGYW who reported high-quality relationships had a lower hazard of pregnancy incidence (caring: HR: 0.79, 95% CI: 0.68, 0.93; closeness: HR: 0.76; 95% CI: 0.64, 0.91). DiscussionPositive caregiver-adolescent relationships are associated with reduced risk of HSV-2 among younger AGYW and pregnancy incidence.

Male circumcision perceptions among HIV vaccine trial participants in Soweto: Qualitative study

Background: Male circumcision has health benefits and cultural significance in South Africa and elsewhere. We sought to understand perceptions about male circumcision among participants enrolled in a preventive human immunodeficiency virus (HIV) vaccine efficacy trial in South Africa.Methods: We conducted a qualitative study with 28 consenting people aged 18–35 years old who self-reported that they were not living with HIV and who were participating in the HIV Vaccine Trials Network (HVTN) 702 vaccine efficacy trial in Soweto. Using a semi-structured guide, we facilitated four focus group discussions (FGDs) stratified by age, gender and sexual orientation. Focus group discussions were audio-recorded, transcribed verbatim, translated into English and thematically analysed.Results: Four main themes emerged: (1) accurate knowledge about what male circumcision is, with some participants stating that it partially reduces acquisition of HIV and sexually transmitted infections; (2) emerging distrust of cultural circumcision because of perceived lack of transparency and adverse events; (3) misperceptions that circumcision boosted masculinity and (4) the influenced of parents, family and female partners in circumcision decision-making.Conclusion: Young South African HIV vaccine trial participants accurately understand the HIV prevention benefits of male circumcision, but uptake decisions are embedded within a context informed by culture, sexuality, masculinity norms and values and the influence of women.Contribution: In this study, we showed that young South Africans participating in HIV vaccine trials instead embed their circumcision uptake decisions within a context informed by culture, sexuality and masculinity norms and values and influence of women.

Interest in Oral Pre-exposure Prophylaxis Among Men Who Have Sex with Men and Transfeminine Persons in HPTN 075, a Multi-center HIV Prevention Study in Sub-Saharan Africa (2015-2017).

Use of oral pre-exposure prophylaxis (O-PrEP) for HIV prevention has not been fully utilized in sub-Saharan Africa, especially among key populations with high HIV incidence and prevalence, including men who have sex with men (MSM) and transgender women (TGW). We examined correlates of interest in O-PrEP among participants in the HIV Prevention Trials Network (HPTN) Study 075, a prospective cohort study, conducted between 2015 and 2017, across 4 sites in Kenya, Malawi, and South Africa. The study included persons assigned male sex at birth, between 18 and 44 years of age, who reported anal intercourse with a man in the past 3 months. Interest in O-PrEP and potential correlates were assessed among 297 participants who were HIV negative. 52% of the participants reported being aware of PrEP and 73% indicated interest in PrEP once informed about it. PrEP interest was not significantly associated with any of the surveyed demographic or psychosocial variables except study site. Our findings suggest a broad and general interest in O-PrEP among MSM and TGW in sub-Saharan Africa, despite relatively low awareness. While the situation around PrEP will have changed in the included countries, major questions about successful implementation still need to be addressed.

Trends in Postpartum Hemorrhage Prevalence and Comorbidity Burden: Insights from the ENACT Network Aggregated Electronic Health Record Data.

The goal of this study was to assess trends in postpartum hemorrhage (PPH), its risk factors, and maternal comorbidity burden in the United States using aggregate data from the Evolve to Next-Gen Accrual to Clinical Trials (ENACT) network. This federated network employs interactive querying of electronic health record data repositories in academic medical centers nationwide. We conducted repeated annual cross-sectional analyses to evaluate PPH occurrence and comorbidities across various ethnoracial and sociodemographic groups, starting with a large cohort of 1,287,675 unique delivery hospitalizations collected from 22 ENACT sites between 2005 and 2022. During this time, there was a statistically significant increasing trend in the prevalence of PPH, rising from 5,634 to 10,504 PPH per 100,000 deliveries (P trend <0.001). Our findings revealed a continuous upward trend in PPH rates that remained consistent among women with ≥ 1 comorbid conditions (P trend <0.001) and those with ≥ 1 maternal risk factor (P trend <0.001). This result aligns with prior studies and extends beyond the time periods previously reported. Overall, Native Hawaiian or Other Pacific Islander women had the highest PPH prevalence (~ 13%), followed by Asian (9.8%), American Indian or Alaska Native (8.9%), multirace (8.6%), Black or African American (8.4%) and White (7.4%) women. The top PPH risk factor identified was placenta previa or accreta, while the top comorbidity was antepartum hemorrhage / placental abruption. The most common cause of PPH, namely uterine atony, was prevalent in ENACT data. Our analysis highlights significant ethnoracial disparities and underscores the need for targeted preventative interventions.

Streamlining the Conduct of Cancer Clinical Trials: New Standard Data Collection Practices for National Cancer Institute Late Phase Clinical Studies.

The increase in the complexity of cancer clinical trials over the past several decades has led to a dramatic growth in trial cost and operational burden. The extent and frequency of data collection, particularly in late phase trials which enroll many participants, have been major contributors to this problem. The Clinical Trials and Translational Research Advisory Committee of the National Cancer Institute (NCI) recently assessed the impact of these stressors on the NCI National Clinical Trials Network (NCTN) and recommended that data collection in late phase NCTN trials be limited to data elements essential to address the primary and secondary objectives of the trial. The purpose of this commentary is to describe the rationale for this recommendation, progress towards implementation, and the development of new streamlined standard practices for data collection for late phase NCTN trials effective January 1, 2025.

Peer Intervention to Link Overdose Survivors to Treatment (PILOT): Protocol for a Multisite, Randomized Controlled Trial Conducted Within the National Institute on Drug Abuse Clinical Trials Network.

The increase in opioid-related overdoses has caused a decrease in average life expectancy, highlighting the need for effective interventions to reduce overdose risk and prevent subsequent overdoses. Peer support specialists (PSSs) offer an appealing strategy to engage overdose survivors and reduce overdose risk, but randomized controlled trials are needed to formalize peer-led interventions and evaluate their effectiveness. This National Institute on Drug Abuse Clinical Trials Network (CTN) study is a multisite, prospective, pilot randomized (1:1) controlled trial (CTN protocol 0107) that aims to evaluate the effectiveness of an emergency department (ED)-initiated, peer-delivered intervention tailored for opioid overdose survivors (PeerIntervention to Link Overdose survivors toTreatment [PILOT]), compared with treatment as usual (TAU). This study evaluates the effectiveness of the 6-month, PSS-led PILOT intervention compared with TAU on the primary outcome of reducing overdose risk behavior 6 months after enrollment. Adults (aged ≥18 years; N=150) with a recent opioid-related overdose were identified and approached in the ED. Participants were screened and enrolled, either in the ED or within 7 days of ED discharge at research offices or in the community and then asked to complete study visits at months 1, 3, 6 (end of intervention), and 7 (follow-up). Participants were enrolled at 3 study sites in the United States: Greenville, South Carolina; Youngstown, Ohio; and Everett, Washington. Participants randomized to the PILOT intervention received a 6-month, PSS-led intervention tailored to each participant's goals to reduce their overdose risk behavior (eg, overdose harm reduction, housing, medical, and substance use treatment or recovery goals). Participants randomized to TAU received standard-of-care overdose materials, education, and services provided through the participating EDs. This paper describes the study protocol and procedures, explains the design and inclusion and exclusion decisions, and provides details of the peer-led PILOT intervention and supervision of PILOT PSSs. Study enrollment opened in December 2021 and was closed in July 2023. A total of 150 participants across 3 sites were enrolled in the study, meeting the proposed sample size for the trial. Primary and secondary analyses are underway and expected to be published in early 2025. There is an urgent need to better understand the characteristics of overdose survivors presenting to the ED and for rigorous trials evaluating the effectiveness of PSS-led interventions on engaging overdose survivors and reducing overdose risk. Results from this pilot randomized controlled trial will provide a description of the characteristics of overdose survivors presenting to the ED; outline the implementation of PSS services research in ED settings, including PSS implementation of PSS supervision and activity tracking; and inform ED-initiated PSS-led overdose risk reduction interventions and future research to better understand the implementation and efficacy of these interventions. ClinicalTrials.gov NCT05123027; https://clinicaltrials.gov/study/NCT05123027. DERR1-10.2196/60277.

Access to Allogeneic Cell Transplantation Based on Donor Search Prognosis: An Interventional Trial.

Patients requiring allogeneic hematopoietic cell transplantation have variable likelihoods of identifying an 8/8 HLA-matched unrelated donor. A Search Prognosis calculator can estimate the likelihood. To determine if using a search algorithm based on donor search prognosis can result in similar incidence of transplant between patients Very Likely (>90%) vs Very Unlikely (<10%) to have a matched unrelated donor. This interventional trial utilized a Search Prognosis-based biologic assignment algorithm to guide donor selection. Trial enrollment from June 13, 2019-May 13, 2022; analysis of data as of September 7, 2023 with median follow-up post-evaluability of 14.5 months. National multi-center Blood and Marrow Transplantation Clinical Trials Network 1702 study of US participating transplant centers. Acute myeloid and lymphoid leukemias, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphomas, severe aplastic anemia, and sickle cell disease patients referred to participating transplant centers were invited to participate. 2225 patients were enrolled and 1751 were declared evaluable for this study. Patients were declared evaluable once it was determined no suitable HLA-matched related donor was available. Patients assigned to the Very Likely arm were to proceed with matched unrelated donor, while Very Unlikely were to utilize alternative donors. A third stratum, Less Likely (∼25%) to find a matched unrelated donor, were observed under standard center practices, but were not part of the primary objective. Cumulative incidence of transplantation by Search Prognosis arm. Evaluable patients included 1751 of which 413 (24%) were from racial/ethnic minorities. Search prognosis was 958 (55%) Very Likely, 517 (30%) Less Likely and 276 (16%) Very Unlikely. 1171 (67%) received HCT, 384 (22%) died without HCT, and 196 (11%) remained alive without HCT. Among the 1,234 patients, the adjusted cumulative incidence (95% CI) of HCT at 6-months was 59.8% (56.7-62.8) in the Very Likely group versus 52.3% (46.1-58.5) in the Very Unlikely (P=0.113). A prospective Search Prognosis-based algorithm can be effectively implemented in a national multicenter clinical trial. This approach resulted in rapid alternative donor identification and comparable rates of HCT in patients Very Likely and Very Unlikely to find a matched unrelated donor. Trial Registration: NCT#03904134.

Epidemiology of cardiogenic shock using the Shock Academic Research Consortium (SHARC) consensus definitions.

The Shock Academic Research Consortium (SHARC) recently proposed pragmatic consensus definitions to standardize classification of cardiogenic shock (CS) in registries and clinical trials. We aimed to describe contemporary CS epidemiology using the SHARC definitions in a cardiac intensive care unit (CICU) population. The Critical Care Cardiology Trials Network (CCCTN) is a multinational research network of advanced CICUs coordinated by the TIMI Study Group (Boston, MA). Cardiogenic shock was defined as a cardiac disorder resulting in SBP < 90 mmHg for ≥30 min [or the need for vasopressors, inotropes, or mechanical circulatory support (MCS) to maintain SBP ≥ 90 mmHg] with evidence of hypoperfusion. Primary aetiologic categories included acute myocardial infarction-related CS (AMI-CS), heart failure-related CS (HF-CS), and non-myocardial (secondary) CS. Post-cardiotomy CS was not included. Heart failure-related CS was further subcategorized as de novo vs. acute-on-chronic HF-CS. Patients with both cardiogenic and non-cardiogenic components of shock were classified separately as mixed CS. Of 8974 patients meeting shock criteria (2017-23), 65% had isolated CS and 17% had mixed shock. Among patients with CS (n = 5869), 27% had AMI-CS (65% STEMI), 59% HF-CS (72% acute-on-chronic, 28% de novo), and 14% secondary CS. Patients with AMI-CS and de novo HF-CS were most likely to have had concomitant cardiac arrest (P < 0.001). Patients with AMI-CS and mixed CS were most likely to present in more severe shock stages (SCAI D or E; P < 0.001). Temporary MCS use was highest in AMI-CS (59%). In-hospital mortality was highest in mixed CS (48%), followed by AMI-CS (41%), similar in de novo HF-CS (31%) and secondary CS (31%), and lowest in acute-on-chronic HF-CS (25%; P < 0.001). SHARC consensus definitions for CS classification can be pragmatically applied in contemporary registries and reveal discrete subpopulations of CS with distinct phenotypes and outcomes that may be relevant to clinical practice and future research.

Impact of COVID-19 on MOUD retention in a sample of rural primary care patients: A secondary analysis of electronic health records

IntroductionThere is limited research examining factors impacting MOUD retention in rural settings, especially within the context of the COVID-19 pandemic. Using electronic health records data collected as part of a NIDA Clinical Trials Network study (CTN-0102), this study explored how the onset of the COVID-19 pandemic may have impacted MOUD retention in a sample of 563 rural primary care patients. MethodsCox regression model was applied to examine if COVID-19 was related to treatment retention, controlling for demographics, clinic, insurance type, and other diagnoses. The independent variable was the number of days between the patient’s first MOUD prescription date during the pre-COVID observation period (10/1/2019–3/13/2020) and the start of the COVID-19 pandemic. The dependent variable was retention on MOUD, defined as the time from the first MOUD prescription documented during the pre-COVID observation period to the first break in consecutive MOUD prescriptions (right censored at 180 days). ResultsThe findings demonstrated that there was a reduced risk of a prescription break for every 10-day increase in the time from the first documented MOUD prescription to the onset of the COVID-19 pandemic (HR = 0.96, 95 % CI = 0.92–0.99; p = 0.011). ConclusionsWhile the data did not include complete treatment histories to determine who was new to MOUD treatment, the findings suggest that patients whose first documented MOUD prescription in the dataset was closer to the onset of the pandemic had a greater likelihood of experiencing retention challenges. This underscores the importance for clinics to establish comprehensive contingency plans for future emergencies to ensure uninterrupted MOUD treatment and support, particularly for individuals in the early stabilization phase of their recovery.

Health-related quality of life with gilteritinib vs placebo posttransplant for FLT3-ITD+ acute myeloid leukemia

AbstractThe Blood and Marrow Transplant (BMT) Clinical Trials Network conducted a phase 3 randomized trial comparing gilteritinib with placebo after allogeneic hematopoietic cell transplantation (HCT) for FLT3-ITD+ acute myeloid leukemia (AML). The primary analysis demonstrated no statistically significant difference in relapse-free survival (RFS); however, patients with FLT3-ITD measurable residual disease (MRD) peri-HCT had significantly longer RFS with gilteritinib. This analysis investigates the effect of post-HCT gilteritinib vs placebo on health-related quality of life (HRQOL). HRQOL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (FACT-Leu), and EuroQOL-5 Dimensions (EQ-5D-5L) at post-HCT randomization; day 29; months 3, 6, 12, 18, 24; and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. HRQOL completion rate was acceptable (>70%) across all time points and measures. There were no differences in HRQOL scores at any time point between cohorts. Clinically meaningful and time to improvement in HRQOL were similar in both arms. Despite higher treatment-emergent adverse effects with gilteritinib, response to the question of being “bothered by side effects of treatment” did not differ between groups. Subgroup analysis of MRD-positive and negative patients demonstrated no differences in HRQOL between arms. For patients with FLT3-ITD+ AML undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. This trial was registered at www.ClinicalTrials.gov as #NCT02997202.