Standard Of Care Arm Research Articles

Effect of door-to-door distribution of HIV self-testing kits on HIV testing and antiretroviral therapy initiation: a cluster randomised trial in Malawi

IntroductionReaching high coverage of HIV testing remains essential for HIV diagnosis, treatment and prevention. We evaluated the effectiveness and safety of door-to-door distribution of HIV self-testing (HIVST) kits in rural...

Does community-based distribution of HIV self-tests increase uptake of HIV testing? Results of pair-matched cluster randomised trial in Zambia

ObjectivesEnding HIV by 2030 is a global priority. Achieving this requires alternative HIV testing strategies, such as HIV self-testing (HIVST) to reach all individuals with HIV testing services (HTS). We...

Pragmatic economic evaluation of community-led delivery of HIV self-testing in Malawi

IntroductionCommunity-based strategies can extend coverage of HIV testing and diagnose HIV at earlier stages of infection but can be costly to implement. We evaluated the costs and effects of community-led...

Home Health Management of Parkinson Disease Deep Brain Stimulation

The travel required to receive deep brain stimulation (DBS) programming causes substantial burden on patients and limits who can access DBS therapy. To evaluate the efficacy of home health DBS postoperative management in an effort to reduce travel burden and improve access. This open-label randomized clinical trial was conducted at University of Florida Health from November 2017 to April 2020. Eligible participants had a diagnosis of Parkinson disease (PD) and were scheduled to receive DBS independently of the study. Consenting participants were randomized 1:1 to receive either standard of care or home health postoperative DBS management for 6 months after surgery. Primary caregivers, usually spouses, were also enrolled to assess caregiver strain. The home health postoperative management was conducted by a home health nurse who chose DBS settings with the aid of the iPad-based Mobile Application for PD DBS system. Prior to the study, the home health nurse had no experience providing DBS care. The primary outcome was the number of times each patient traveled to the movement disorders clinic during the study period. Secondary outcomes included changes from baseline on the Unified Parkinson's Disease Rating Scale part III. Approximately 75 patients per year were scheduled for DBS. Of the patients who met inclusion criteria over the entire study duration, 45 either declined or were excluded for various reasons. Of the 44 patients enrolled, 19 of 21 randomized patients receiving the standard of care (mean [SD] age, 64.1 [10.0] years; 11 men) and 23 of 23 randomized patients receiving home health who underwent a minimum of 1 postoperative management visit (mean [SD] age, 65.0 [10.9] years; 13 men) were included in analysis. The primary outcome revealed that patients randomized to home health had significantly fewer clinic visits than the patients in the standard of care arm (mean [SD], 0.4 [0.8] visits vs 4.8 [0.4] visits; P < .001). We found no significant differences between the groups in the secondary outcomes measuring the efficacy of DBS. No adverse events occurred in association with the study procedure or devices. This study provides evidence supporting the safety and feasibility of postoperative home health DBS management. ClinicalTrials.gov Identifier: NCT02474459.

A Randomized Controlled Study of Extracorporeal Photopheresis (ECP) Therapy with UVADEX® (Methoxsalen) for National Institutes of Health (NIH)-Graded Moderate to Severe Chronic Graft-Vs-Host Disease (cGVHD)

A Randomized Controlled Study of Extracorporeal Photopheresis (ECP) Therapy with UVADEX® (Methoxsalen) for National Institutes of Health (NIH)-Graded Moderate to Severe Chronic Graft-Vs-Host Disease (cGVHD)

Atorvastatin As an Adjunct Therapy in Patients with Acute Venous Thromboembolism

Background:Venous thromboembolism (VTE) has an estimated incidence of 1-2 per 1000. Despite anticoagulation, many patients suffer from its complications: VTE recurrence rate after an unprovoked VTE is 30%, and the rate of post-thrombotic syndrome is 25-50%. Statins are commonly used for cardiovascular diseases, and their anti-inflammatory properties have been shown to improve clot resolution in mouse models. Therefore, it could be a potential adjunct therapy for acute VTE to expedite clot resolution and reduce morbidities. Here we report initial data of a randomized open label study to investigate the effect of statins on biomarkers and clinical outcomes in patients with acute VTE.Objectives:To evaluate the effect of atorvastatin on thrombin generation, biomarkers and clinical outcomes in patients with acute VTE receiving anticoagulation. We hypothesize that the addition of atorvastatin can reduce thrombin generation and inflammation.Patients/Methods:Adult patients with newly diagnosed acute proximal acute proximal deep vein thrombosis (DVT) +/- pulmonary embolism (PE) were enrolled and randomized 1:1 to standard of care (SOC) (anticoagulation), or SOC plus atorvastatin 40 mg daily. Patients were enrolled within 21 days an acute VTE diagnosis. Fasting blood samples were drawn on enrollment, 3 months, and 9 months, for routine blood tests, thrombin generation, selective cytokines and lipidomic profiles. Clinical outcomes were monitored, including recurrent venous or arterial thromboses, major bleeding events, and post thrombotic symptoms evaluated by the Villalta score. Patients were excluded if they received thrombolysis or statins within 6 weeks prior to enrollment, had malignancy diagnosed within 2 years, pregnant or lactating. Thrombin generation assays were performed using a commercial kit (TECHNOTHROMBIN® TGA, Technoclone, Vienna, Austria) according to the manufacturer's instructions. Parameters recorded included peak thrombin concentration and endogenous thrombin potential (ETP). Two sample t-test were used to compare the differences of two arms with alpha of 0.05.Results:From February 2015 to June 2017, twenty patients were enrolled. Ten were randomized to each arm, SOC vs SOC+statin. The baseline characteristics are summarized in Table 1. The median age is 55.5 years, 50% are female, and 80% are Caucasians. All patients had proximal lower extremity DVT, while 4 (20%) had concurrent PE. All patients have completed 3 month follow-up and 17 (85%) have completed 9 month visits. Eleven patients (55%) were treated with warfarin, the remainder with rivaroxaban. Duration of anticoagulation was at the discretion of the treating physician, with seven patients (35%) continuing on anticoagulation at the most recent visit, resulting in a median duration of anticoagulation to be 6.1 (range 3.3-11.1) months. Two patients were lost to follow-up after the 3 month visit, and two refused the 9-month blood draw. No patients had recurrent VTE or major bleeding on study. Seven (70%) patients on SOC arm compared to 8 (80%) on SOC+statin arm had residual chronic DVT noted on ultrasound at 3 months. The median Villalta score for the affected extremity on enrollment for each arm was 5.5 vs 4.5 (SOC vs SOC+statin), and 4.5 vs 3.5 at 3 months. The mean LDL at 3 months is significantly reduced in patients on statin arm compared to SOC arm, while other markers are not different (Table 2).Figure 1 shows the differences between SOC and SOC+statin by ETP and peak thrombin, separated by visits. There are no significant differences between SOC and SCO+statin arms (Figure 1). Patients have higher thrombin peak and ETP at visit 3 (9 month visit) in both arms, which may be explained by 8 of 13 patients being off anticoagulation at visit 3. When analysis is done based on anticoagulation status at visit 3, reduced peak thrombin and ETP are found in patients on anticoagulation compared to those who are not.Conclusions:In this small pilot study, atorvastatin 40 mg daily did not reduce thrombin generation at 9 months, when used in combination with standard anticoagulation as treatment for an acute VTE. At present the study is limited by the small sample size due to slow recruitment. Atorvastatin did reduce LDL, and may alter inflammatory states, and further analyses of inflammatory markers and lipidomic are ongoing to evaluate the effect of atorvastatin on VTE-related inflammation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparison of the Effects of the Thrombopoietin (TPO) Receptor Agonist Romiplostim in Patients with Immune Thrombocytopenia (ITP) for ≤1 Year Vs. >1 Year

Comparison of the Effects of the Thrombopoietin (TPO) Receptor Agonist Romiplostim in Patients with Immune Thrombocytopenia (ITP) for ≤1 Year Vs. >1 Year

Prevention of Morbidity in Sickle Cell Disease Phase II (Improvement of Cognition in children with Sickle Cell Disease with Auto-adjusting Continuous Positive Airways Pressure: Phase II) (POMS 2b paediatric cohort)

▪Background: Complications in sickle cell anemia (SCA, HbSS) include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation. These effects can be compounded by obstructive sleep apnea (OSA).However, there is concern that oxygen supplementation in SCA may lead to bone marrow suppression. Continuous Positive Airways Pressure (CPAP) is an accepted treatment for OSA in the general population and prevents dips in oxygen saturation.. The aim of this single-blind, randomised, controlled phase II trial is to compare Auto-adjusting CPAP (APAP) with standard care to standard care alone in subjects with HbSS to determine whether the intervention is safe and improves Cancellation, a measure of selective attention and processing speed.Methods: Eligibility criteria included ability to provide informed consent, age >8 and <16 years, diagnosis of HbSS and mean overnight saturation of <90% for <30% of the night. Key exclusion criteria were overnight respiratory support, respiratory or decompensated cardiac failure, chronic transfusion or contra-indications to APAP therapy or MRI.Minimisation/stratification factors were age group (8-11, 12-15 years), silent infarction on MRI, minimum overnight oxygen saturation >90% or <90%, and hydroxyurea (HU) use.APAP adherence was defined as using APAP for an average of 4 hours a night for >50% of the time and was recorded using software documenting hours of use each night. Participant support in terms of appropriate facemask and facilitating adherence were provided by an unblinded sleep physiologist.Full blood counts were obtained at baseline, 2 weeks, 3 months and 6 months.Data were analysed by intention-to-treat. The primary outcome is change in the Cancellation subtest from the Wechsler scales, and secondary outcomes include general cognitive functioning, assessed at baseline and after 6 months of treatment by assessors blind to treatment assignment. Analysis of Covariance (ANCOVA) models, adjusted for minimisation factors, were used to calculate least-square mean changes from baseline to 6 months.Results: 30 children (18 boys; median age 12.5; range 7.9-16 years) with SCA were randomised to standard care + APAP (n=15) or standard care alone (n=15) for 6 months. One child in the standard care alone arm withdrew after 6 weeks, and 8 children in the APAP arm were not adherent to treatment. Increase in cancellation score was numerically greater in the APAP arm (mean 1.46, SE 0.59 vs 1.01, SE 0.61) but this was not significant (mean difference 0.44, 95% CI: -1.42; 2.31; p=0.626). Increase in Cancellation score was greater (mean 2.63; 95%CI: 0.95, 4.30) in those whose adherence was in the highest quartile (> 2.4 hours/night) compared with the other 3 quartiles (mean 0.71, 95%CI: -0.32, 1.75; mean difference 1.91, 95%CI: -0.06, 3.88; p=0.057). In subjects assigned to APAP, cancellation scores were significantly higher with hydroxyurea use (p=0.01). There was no evidence of decline in haemoglobin in either group; hydroxyurea use was associated with an increase in haemoglobin (p=0.01). There were 7 subjects with serious adverse events in the standard care alone arm, compared to 3 in the APAP + standard care arm, all related to hospital admission for pain.Discussion: APAP for 6 months is feasible and safe in children with SCA. Alhough >50% were not adherent by the pre-defined definition, those who were compliant appeared to have more benefit in terms of improvement in attention/processing speed. There appears to be an interaction with HU use, consistent with the importance of oxygen supply and carriage for brain function. If delivery of the intervention can be improved, avoidance of oxygen desaturation with overnight respiratory support alongside HU use may play a role in improving cognition in SCD. DisclosuresNo relevant conflicts of interest to declare.

Prevention of Morbidity in Sickle Cell Disease Phase II (Improvement of Pain and Quality of Life in Children with Sickle Cell Disease with Auto-adjusting Continuous Positive Airways Pressure: Phase II) (POMS 2b pediatric cohort)

▪AbstractBackground: In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation. These effects can be compounded by obstructive sleep apnoea (OSA). Continuous Positive Airways Pressure (CPAP) is an accepted treatment for OSA in the general population. However, supplementary oxygen therapy in SCA may lead to bone marrow suppression. The aim of this single-blind, randomised, controlled phase II trial is to compare Auto-adjusting CPAP (APAP) with standard care to standard care alone in subjects with HbSS to determine whether the intervention is safe and improves attention and processing speed and brain structure.Methods: Eligibility criteria included ability to provide informed consent, age >8 and <16 years, diagnosis of HbSS and mean overnight saturation of <90% for <30% of the night. Key exclusion criteria were overnight respiratory support, respiratory or decompensated cardiac failure, chronic transfusion or contra-indications to APAP therapy or MRI.Minimisation factors were age group (8-11, 12-15), silent infarction on MRI, minimum overnight oxygen saturation > or < 90%, and hydroxyurea (HU) use.APAP adherence was defined as using APAP for an average of 4 hours a night for >50% of the time and was recorded using software documenting hours of use each night. Participant support in terms of appropriate facemask and facilitating adherence were provided by an unblinded sleep physiologist.Full blood counts were obtained at baseline, 2 weeks, 3 months and 6 months.Data were analysed by intention-to-treat. The primary outcome is change in the cancellation subtest from the Wechsler scales, and secondary outcomes include general cognitive functioning, assessed at baseline and after 6 months of treatment by assessors blind to treatment assignment. Analysis of Covariance (ANCOVA) models, adjusted for minimisation factors, were used to calculate least-square mean changes from baseline to 6 months.Results: 30 children with HbSS were randomised to standard care + APAP (n=15) or standard care alone (n=15) for 6 months. One child in the standard care arm withdrew after 6 weeks, and 8 children in the APAP arm were not adherent to treatment. There was no difference in hemoglobin change between the arms, but hydroxyurea use was associated with an increase in haemoglobin (p=0.01). Increase in cancellation score was numerically greater in the APAP arm (mean 1.46, SE 0.59 vs 1.01, SE 0.61) but this was not significant (mean difference 0.44, 95% CI: -1.42; 2.31; p=0.626). Increase in cancellation score was greater (mean 2.63; 95%CI: 0.95, 4.30) in those whose adherence was in the highest quartile (> 2.4 hours/night) compared with the other 3 quartiles (mean 0.71, 95%CI: -0.32, 1.75; mean difference 1.91, 95%CI: -0.06, 3.88; p=0.057). In subjects assigned to APAP, cancellation scores were significantly higher with hydroxyurea use (p=0.01). There were 7 subjects with serious adverse events in the placebo group, compared to 3 in the APAP group, all related to SCD pain. There was no evidence of decline in haemoglobin in either group.Discussion: APAP for 6 months is safe, and feasible in children with SCA but although >50% were not adherent by the pre-defined definition, those who were compliant appeared to have more benefit in terms of attention/processing speed. If delivery of the intervention can be improved, avoidance of oxygen desaturation with overnight respiratory support may play a role in improving cognition in SCD.Trial registration: ISRCTN 46012373 10th July 2015Protocol Version: 6.0 Date: 24th December 2015Sponsor: University Hospital Southampton Sponsor's protocol code: RHMCHIOT53Keywords Sickle Cell Anaemia; haemoglobin oxygen saturation; Auto-adjusting Continuous Positive Airways Pressure; Cancellation; Attention; Processing speed DisclosuresNo relevant conflicts of interest to declare.

The transient effect of a peer support intervention to improve adherence among adolescents and young adults failing antiretroviral therapy in Harare, Zimbabwe: a randomized control trial

BackgroundAdolescents and young adults living with HIV in sub Saharan Africa are at high risk of poor adherence to antiretroviral therapy (ART) and virologic failure (VF).MethodsWe conducted a randomized control trial among adolescents and young adults on ART with VF to assess the effectiveness of a community-based peer support intervention aimed at improving VF. Viral load (VL) levels were obtained at 12, 24 and 36 weeks. A subset of the participants had baseline HIV drug resistance (HIVDR) genotyped using Sanger sequencing.ResultsThe participants’ median (interquartile range (IQR)) age was 18.1 (IQR: 15.1–20.0) years and half (50.5%, n = 107) were male. At week 24, the proportion of subjects with a detectable viremia was significantly lower in the intervention arm than in the standard of care (SOC) arm (76.0% (n = 79) vs. 89.0% (n = 96), p = 0.013). At Week 36, there remained a difference in the proportion of subjects with a detectable VL between the intervention arm (68.3%, n = 71) and SOC arm (79.6%, n = 86), which was trending towards statistical significance (p = 0.059). There was no difference in the probability of having a detectable VL over time between the intervention and SOC groups (adjusted odds ratio: 1.14, p = 0.439). Baseline HIVDR was observed in 44.0% of the participants in the intervention and 56.0% in the SOC group (p = 0.146).ConclusionA transient effect of the peer support intervention in improving VF was observed among adolescents and young people failing ART.Trial registration: This study is registered with www.clinicaltrials.gov under the reference number: NCT02833441

CORonavirus-19 mild to moderate pneumonia Management with blood Ozonization in patients with Respiratory failure (CORMOR) multicentric prospective randomized clinical trial

BackgroundFollowing positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia. MethodsThe trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT). ResultsA total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients).The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p = 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease.No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤ 5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0–1] in the SoC arm vs. 2 [1–3] the O3-AHT arm; p = 0.018). No adverse events related O3-AHT treatment was observed. ConclusionIn mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results.

Engaging People Who Inject Drugs Living With HIV in Antiretroviral Treatment and Medication for Opioid Use Disorder: Extended Follow-up of HIV Prevention Trials Network (HPTN) 074.

BackgroundPeople who inject drugs (PWID) living with HIV experience inadequate access to antiretroviral treatment (ART) and medication for opioid use disorders (MOUD). HPTN 074 showed that an integrated intervention increased ART use and viral suppression over 52 weeks. To examine durability of ART, MOUD, and HIV viral suppression, participants could re-enroll for an extended follow-up period, during which standard-of-care (SOC) participants in need of support were offered the intervention.MethodsParticipants were recruited from Ukraine, Indonesia and Vietnam and randomly allocated 3:1 to SOC or intervention. Eligibility criteria included: HIV-positive; active injection drug use; 18-60 years of age; ≥1 HIV-uninfected injection partner; and viral load ≥1,000 copies/mL. Re-enrollment was offered to all available intervention and SOC arm participants, and SOC participants in need of support (off-ART or off-MOUD) were offered the intervention.ResultsThe intervention continuation group re-enrolled 89 participants, and from week 52 to 104, viral suppression (<40 copies/mL) declined from 41% to 29% (estimated 9.4% decrease per year, 95% CI -17.0%; -1.8%). The in need of support group re-enrolled 94 participants and had increased ART (re-enrollment: 55%, week 26: 69%) and MOUD (re-enrollment: 16%, week 26: 25%) use, and viral suppression (re-enrollment: 40%, week 26: 49%).ConclusionsViral suppression declined in year 2 for those who initially received the HPTN 074 intervention and improved maintenance support is warranted. Viral suppression and MOUD increased among in need participants who received intervention during the study extension. Continued efforts are needed for widespread implementation of this scalable, integrated intervention.

OP35 Effect of maintenance ustekinumab on corticosteroid-free endoscopic and clinical outcomes in patients with Crohn’s Disease - Week 48 analysis of the STARDUST trial

Abstract Background The STARDUST study demonstrated that ustekinumab (UST), using either a treat-to-target (T2T) or standard of care (SoC) strategy, may induce and maintain endoscopic and clinical response and remission in Crohn’s disease (CD). Primary endpoint, safety, and efficacy have been reported previously.1 Because corticosteroid (CS) sparing is an important aim of CD management, we compared the efficacy of UST T2T vs SoC in achieving CS-free clinical remission and endoscopic response. Methods Adult patients (pts) with moderate–severely active CD who were CDAI 70 responders after 16 weeks (W) of induction, comprising a single dose of UST 6 mg/kg iv followed by UST 90 mg SC at W8, were randomized to either T2T or SoC arms. In the T2T arm, choice of UST maintenance dosage (q12w or q8w) was based on endoscopic improvement at W16, followed by clinical and biomarker-directed dose escalation up to q4w; in the SoC arm, UST q12w or q8w dosage was based on EU SmPC. Primary endpoint was endoscopic response (Simple Endoscopic Score in CD [SES-CD] decrease from baseline [BL] ≥50%) at W48. For pts on CS at W16, CS tapering was mandatory. At W48, CS-free clinical remission (CDAI &amp;lt;150 and no CS for ≥30 days) and CS-free endoscopic response (reduction from BL in SES-CD ≥50% and no CS for ≥30 days) were evaluated. Results Of 500 pts enrolled, 441 achieved a CDAI 70 response at W16 and were randomized to T2T (n=220) or SoC (n=221); 79.1% and 87.3%, respectively, completed W48. Among clinical remitters and responders at W16 (start of CS tapering), in both T2T and SoC arms more than 70% were still in remission or response at W48 (Figure 1). CS use throughout 48 weeks of treatment is summarized in Table 1. At W48, in T2T and SoC arms similar rates were noted for CS-free endoscopic response (33.6% and 28.5%, respectively) and CS-free clinical remission (56.4% and 63.3%, respectively). Notably, in T2T and SoC arms the CS-free clinical remission rate among pts on CS at BL was 44.1% and 45.1%, respectively (Figure 2). Among W48 endoscopic responders (T2T, n=83; SoC, n=66), CS-free endoscopic response rate was 89.2% and 95.5%, respectively; among W48 clinical remitters (T2T, n=135; SoC, n=154), CS-free clinical remission rate was 91.9% and 90.9%, in T2T and SoC arms, respectively. Conclusion Pts treated with UST under T2T or SoC strategies achieved similar rates of CS-free clinical remission and endoscopic response over 48 weeks. Overall for pts on CS at BL, UST reduced the need for CS while achieving response/remission. Most (&amp;gt;89%) pts with endoscopic response/clinical remission at W48 were also CS-free responders/remitters. Reference

P301 Ustekinumab improves health-related quality of life in patients with moderate-to-severe Crohn’s disease: results up to Week 48 of the STARDUST trial

Abstract Background A treat-to-target (T2T) strategy may optimize inflammatory bowel disease management. The STARDUST trial compared a T2T maintenance strategy against standard of care (SoC) in Crohn’s disease (CD) patients treated with ustekinumab (UST). The primary endpoint, safety, and efficacy data of STARDUST have been published previously.1 Here we present results for health-related quality of life (HRQoL) measures and impact of UST on work and activities at Week (W)48 of UST maintenance, comparing T2T and SoC. Methods Adult patients with moderate–severely active CD received iv, weight-based UST ~6 mg/kg at W0 (baseline [BL]); then SC UST 90 mg at W8. At W16, CD activity index (CDAI) 70 responders were randomized (1:1) to either T2T (maintenance dosing, q12w or q8w, assigned based on endoscopic activity and further dose escalations up to q4w if clinical and biomarker-directed targets were not met) or SoC (maintenance based on EU SmPC; q12w or q8w based on clinical judgement). In this analysis we assessed changes from BL in the following HRQoL measures at W48: Inflammatory Bowel Disease Questionnaire (IBDQ), EuroQoL 5 Dimension 5 Level (EQ-5D-5L), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) tools, and Hospital Anxiety and Depression Scale – anxiety and depression subscales (HADS-A and -D) alongside the Work Productivity and Activity Impairment (WPAI) questionnaire; time lost from work was also recorded. Percentage of patients with IBDQ response (16 point improvement from BL) and remission (IBDQ score ≥170) at W48 were also analysed. Results Of 500 patients enrolled, 441 were randomized to T2T (n=220) or SoC (n=221); 79.1% and 87.3%, respectively, completed W48. At W48, the percentage of patients in T2T and SoC arms with IBDQ response (58.2% and 67.0%, respectively) and remission (45.0% and 53.4%, respectively) were similar (both p=ns). Similar changes from BL at W48 in IBDQ, EQ-5D-5L (visual analogue scale and index score), FACIT-F, HADS-A and -D and WPAI were noted in both treatment arms (Table 1). WPAI 7-Point Improvement from BL per domain at W48 are presented in Table 2. During the last 4 weeks preceding the visit at W48, patients in T2T and SoC arms on average lost 1.7 and 2.2 fewer days from work due to CD, respectively, compared to BL (p=ns). At W48, 62.3% and 72.3% were in employment in T2T and SoC arms, respectively (p=ns), compared to 61.8% and 63.5%, respectively at BL. Conclusion UST treatment improved HRQoL and work productivity and helped decrease time lost from work in patients with moderate-to-severe CD, regardless of T2T or SoC strategy. Improvements were generally maintained up to W48. Reference

OP40 Analysis of clinical features associated with favourable outcomes from ustekinumab treat-to-target strategy in Crohn’s Disease patients in the STARDUST trial

Abstract Background The 48-week (W) interventional STARDUST trial assessed whether a treat-to-target (T2T) strategy using ustekinumab (UST) may optimize Crohn’s disease (CD) outcomes; primary efficacy and safety data have been reported before.1 Here we assessed which patient (pt) subgroups may benefit from T2T vs standard of care (SoC) in achieving endoscopic response after 1 year of UST treatment. Methods Adult pts with moderate–severely active CD (CD activity index [CDAI] 220–450) and Simple Endoscopic Score in CD [SES-CD] ≥3) who failed conventional therapy and/or 1 biologic were included. Pts received iv, weight-based UST ~6 mg/kg at W0 (baseline [BL]); then SC UST 90 mg at W8. At W16, CDAI 70 responders were randomized (1:1) to T2T or SoC arms. Pts in the T2T arm were assigned to SC UST q12w or q8w based on 25% improvement in SES-CD score vs BL. From W16–48, UST dose was further intensified up to q4w if the following were not met: CDAI &amp;lt;220 and ≥70-point improvement from BL, and C-reactive protein ≤10 mg/L or faecal calprotectin (FCal) ≤250 µg/g. Pts who failed treatment target despite UST q4w were discontinued. In the SoC arm, UST dose was assigned based on EU SmPC (q12w or q8w). We report the treatment effect for the primary endpoint (endoscopic response [≥50% improvement in SES-CD score vs BL] at W48), evaluated for subgroups of pts, based on demographics at BL. For each subgroup, the odds ratio (OR) and 95% confidence interval (CI) of T2T vs SoC were provided based on the logistic regression model that included treatment arm and stratification factors (prior exposure to biologics [none or 1] and SES-CD score [≤16, &amp;gt; 16] at BL) as independent variables. Results Of 500 pts enrolled, 441 were randomized to T2T (n=220) or SoC (n=221); 79.1% and 87.3% completed W48. At W48, pts randomized to T2T were more likely to achieve endoscopic response compared to SoC (p&amp;lt;0.05), if they had at BL: (i) longer disease duration (&amp;gt;median [79.1 months]; OR 2.2; 95%CI 1.17–3.94); (ii) clinically moderate disease (CDAI ≤300; OR 1.7; 95%CI 1.03–2.76); (iii) normal FCal (≤250; OR 3.0; 95%CI 1.22–7.56), (iv) endoscopically active CD (SES-CD ≥4 for ileal or ≥6 for colonic and/or ileocolonic disease; OR 1.8; 95%CI 1.10–2.91); and (v) history or presence of strictures/fistula or occurrence of an intra-abdominal abscess (OR 2.3; 95%CI 1.06–5.01 and OR 3.5; 95%CI 1.07–11.19, respectively; Figure 1). Conclusion T2T was more effective than SoC (p&amp;lt;0.05) in achieving endoscopic response after 1 year of UST treatment in certain subgroups including pts with higher endoscopic scores at BL and those with history/presence of bowel damage. Reference

Phase III study of local or systemic therapy INtensification DIrected by PET in prostate CAncer patients with post-prostaTEctomy biochemical recurrence (INDICATE): ECOG-ACRIN EA8191.

TPS5098 Background: Radiation therapy (RT) to the prostate bed and pelvic nodes with short-term androgen deprivation therapy (STAD) is considered a standard of care (SOC) salvage therapy (ST) paradigm for prostate cancer (PC) patients (pts) with post-prostatectomy (RP) biochemical recurrence (BCR). Fluciclovine-PET/CT imaging is FDA-approved in this setting, with improved accuracy for detection of metastases not identified with conventional imaging (CIM). Given PET's greater sensitivity and specificity, its findings are increasingly but variably applied to justify modification or omission of SOC therapies without high-level evidence of clinical benefit. PET may help identify candidates for local or systemic treatment intensification of the otherwise non-tailored SOC approach. Improved systemic control and disease detection with molecular imaging have led to increasing use of focally ablative metastasis-directed RT, to delay or enhance systemic therapy through increased local control. There is also interest in earlier use of systemic therapy; apalutamide (Apa) is a nonsteroidal antiandrogen with established efficacy in improving overall and radiographic progression-free survival (PFS) for non-metastatic castration-resistant and metastatic castration-sensitive PC. This study will evaluate whether pts with PET-detected lesions benefit from such local or systemic treatment intensification approaches. Methods: PC pts with post-RP BCR (PSA&gt;0.5ng/mL; &gt;0.2ng/mL if within 12 mos of RP) and no metastases on CIM who are candidates for SOC ST (RT to prostate bed and pelvic nodes with STAD) are eligible. Prior to study registration, pts undergo SOC baseline PET (18F-fluciclovine but PSMA radiotracers permitted pending commercial availability). Based on institutional clinical interpretation of the SOC PET, pts will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic metastases). Cohort 1 will be randomized to SOC ST +/- Apa for 6 months and Cohort 2 will be randomized to SOC ST and Apa +/- metastasis-directed RT to PET-positive lesions. The primary endpoint is PFS, defined as time from randomization to radiographic progression on CIM, symptomatic disease or death. Primary objectives are to evaluate whether addition of Apa to SOC ST and addition of metastasis-directed RT to SOC ST and Apa could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 pts will be randomized with 85% power to distinguish 5-year PFS rate of 90% (Apa arm) vs. 80% (SOC arm) using one-sided stratified log-rank test with type I error of 0.025. For Cohort 2, 324 pts will be randomized with 85% power to distinguish 5-year PFS rate of 76.5% in the experimental arm from 61.5% in the control arm. Secondary endpoints include overall and event-free survival, toxicity, and PET progression. Clinical trial information: NCT04423211.

Phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non-small cell lung cancer previously treated with a checkpoint inhibitor: Toxicity update (Lung-MAP non-matched sub-study S1800A).

9075 Background: The therapeutic landscape in metastatic NSCLC has dramatically changed with approvals of immunotherapy agents in both treatment-naïve and previously treated cancer patients (pts) and irrespective of histology. Pts with tumors that develop resistance is a significant area of unmet need. Vascular endothelial growth factor (VEGF) has been shown to modulate the tumor immune microenvironment and combination immune checkpoint and VEGF/VEGF receptor inhibition have shown benefit in multiple tumor types. Lung-MAP is a master protocol for pts with stage IV, previously treated NSCLC. Pts who were not eligible for a biomarker-matched substudy enrolled in S1800A. The adverse event profile will be presented. Methods: S1800A is a phase II randomized trial for pts who previously received PD-1 or PD-L1 inhibitor therapy for at least 84 days and platinum-based doublet therapy with ECOG 0-1 stratified by PD-L1 expression, histology and intent to receive ramucirumab in the standard of care (SOC) arm. Pts were randomized 1:1 to pembrolizumab and ramucirumab P+R or SOC (docetaxel +R [SOC w R]; docetaxel, pemetrexed or gemcitabine [SOC wo R]). The primary endpoint was overall survival. Secondary endpoints included response, duration of response, investigator assessed-progression free survival and evaluation of toxicity. Results: From May 17, 2019 to November 16, 2020, 166 pts enrolled and 140 determined eligible [69 (49%) P+R; 46 (33%) SOC w R; 25 (18%) SOC wo R]. Treatments for those who received SOC wo R included 3 on docetaxel (19%); 12 on gemcitabine (75%); and on 1 on pemetrexed (6%). 131 were eligible for adverse event (AE) assessment. The most common AE were fatigue (38%), proteinuria (28%), hypertension (23%), diarrhea (22%) and hypothyroidism (22%) on P+R; fatigue (61%), anemia (48%), diarrhea (41%) and neutropenia (39%) on SOC w R and anemia (56%), leukopenia (56%), fatigue (44%) and neutropenia (44%) on SOC wo R. Grade ≥ 3 treatment-related AEs occurred in 32% of pts on P+R, 54% of pts on SOC w R and 56% of pts on SOC wo R. Cardiac and thromboembolic events occurred in 12% of pts on P+R, 11% of pts on SOC w R and 0% of pts on SOC wo R. Grade 5 AE occurred in 2 pts on P+R (respiratory failure and cardiac arrest), 3 pts on SOC w R (2 respiratory failure and sepsis) and 1 pt on SOC wo R (sepsis). Four patients were diagnosed with COVID-19 (1 on P+R and 3 on SOC) and 3 died (1 on P+R and 2 on SOC). Conclusions: Grade 3 toxicities were lower in P+R compared to SOC arms with or without R. Cardiac and thromboembolic events were similar in arms that included R. P+R was generally well-tolerated. Efficacy outcomes will be presented when data matures. Clinical trial information: NCT03971474.

Exploring the feasibility of using real-world data from a large clinical data research network to simulate clinical trials of Alzheimer\u2019s disease

In this study, we explored the feasibility of using real-world data (RWD) from a large clinical research network to simulate real-world clinical trials of Alzheimer’s disease (AD). The target trial (i.e., NCT00478205) is a Phase III double-blind, parallel-group trial that compared the 23 mg donepezil sustained release with the 10 mg donepezil immediate release formulation in patients with moderate to severe AD. We followed the target trial’s study protocol to identify the study population, treatment regimen assignments and outcome assessments, and to set up a number of different simulation scenarios and parameters. We considered two main scenarios: (1) a one-arm simulation: simulating a standard-of-care (SOC) arm that can serve as an external control arm; and (2) a two-arm simulation: simulating both intervention and control arms with proper patient matching algorithms for comparative effectiveness analysis. In the two-arm simulation scenario, we used propensity score matching controlling for baseline characteristics to simulate the randomization process. In the two-arm simulation, higher serious adverse event (SAE) rates were observed in the simulated trials than the rates reported in original trial, and a higher SAE rate was observed in the 23 mg arm than in the 10 mg SOC arm. In the one-arm simulation scenario, similar estimates of SAE rates were observed when proportional sampling was used to control demographic variables. In conclusion, trial simulation using RWD is feasible in this example of AD trial in terms of safety evaluation. Trial simulation using RWD could be a valuable tool for post-market comparative effectiveness studies and for informing future trials’ design. Nevertheless, such an approach may be limited, for example, by the availability of RWD that matches the target trials of interest, and further investigations are warranted.

Midregional proadrenomedullin safely reduces hospitalization in a low severity cohort with infections in the ED: a randomized controlled multi-centre interventional pilot study

IntroductionThe midregional fragment of proadrenomedullin (MR-proADM) is known to provide accurate short-, mid- and long term prognostic information in the triage and multi-dimensional risk assessment of patients in the emergency department (ED). In two independent observational cohorts MR-proADM values identified low disease severity patients without risk of disease progression in the ED with no 28 days mortality that wouldn´t require hospitalization. In this interventional study we want to show that the combination of an MR-proADM algorithm with clinical assessment is able to identify low risk patients not requiring hospitalization to safely reduce the number of hospital admissions. MethodsA randomized-controlled interventional multicenter study in 4 EDs in Spain. The study protocol was approved by Ethics Committees. Control arm patients received Standard Care. MR-proADM guided arm patients with low MR-proADM value (≤0.87 nmol/L) were treated as out-patients, with high MR-proADM value (>0.87 nmol/L) were hospitalized. The hospitalization rate was compared between the study arms. ResultsTwo hundred patients with suspicion of infection were enrolled. In the MR-proADM guided arm the hospital admission rate in the intention-to-treat (ITT) population was 17% lower than in the control arm (40.6% vs. 57.6%, p=0.024) and 20% lower in the per protocol (PP) population (37.2% vs. 57.6%, p=0.009). No deaths of out-patients and no significant difference for the safety endpoints readmission and representation rates were observed. The readmission rate was only slightly higher in the MR-proADM guided arm compared to the control arm (PP population: at 14 days 9.3% vs. 7.1%, difference 2.1% (95% CI: -11.0% to 15.2%); and at 28 days 11.1% vs. 9.5%, difference 1.6% (95% CI: -12.2% to 15.4%)). The rate of 28 days representation was slightly lower in the MR-proADM guided arm compared to the control arm (20.4% vs. 26.2%, difference -5.8% (95% CI: -25.0% to 13.4%); PP population). ConclusionsImplementing a MR-proADM algorithm optimizes ED workflows efficiently and sustainably. Hospitals can highly benefit from a reduced rate of hospitalizations by 20% using MR-proADM. The safety in the MR-proADM guided study arm was similar to the Standard Care arm. Trial registrationClinicalTrials.gov Identifier NCT03770533

Treatment of mild-to-moderate pelvic inflammatory disease with a short-course azithromycin-based regimen versus ofloxacin plus metronidazole: results of a multicentre, randomised controlled trial

ObjectiveA multicentre, randomised non-inferiority trial compared the efficacy and safety of 14 days of ofloxacin and metronidazole (standard-of-care (SoC)) versus a single dose of intramuscular ceftriaxone followed by 5 days...