Total mesorectal excision (TME) is highly effective for early-stage rectal cancer, but is associated with considerable morbidity, which can substantially impair the quality of life (QoL) of patients. For very early tumours (low-risk cT1), local excision (LE) offers the possibility of organ preservation (OP) with reduced morbidity; however, its application is limited to a selected group. For early tumours where upfront LE is not feasible, primary OP with (chemo)radiotherapy as an alternative to TME surgery has been evaluated in the STARTREC phase II/III studies, which reported promising 1-year OP rates.

The STARTREC-3 trial aims to increase the 2-year OP rate from 60% to 80% in early rectal cancer (cT1–3abN0) and from 30% to 60% in early-intermediate rectal cancer (cT1–3abN1, ≤3 mesorectal nodes measuring ≤8 mm) by intensifying neoadjuvant treatment in different study arms.

STARTREC-3 is embedded in the STARTREC master trial protocol, which uses an adaptive platform study design allowing early termination of inferior treatment arms and the addition of novel arms. The multicentre STARTREC-3 trial investigates three parallel, non-comparative treatment strategies for patients with early and early-intermediate rectal adenocarcinoma who prefer OP over primary TME surgery. All arms start with 5x5 Gy radiotherapy, followed by: an endoluminal boost via contact X-ray brachytherapy (arm 1), an external beam radiotherapy (EBRT) boost by MR-guided EBRT (arm 2) or three cycles of capecitabine oxaliplatin systemic treatment chemotherapy (arm 3). Treatment allocation is predefined and centre-dependent. Response evaluations (MRI and endoscopy) are planned at 14–16 weeks and 26 weeks after onset of radiotherapy. The primary endpoint is the proportion of patients with successful OP at 24 months from onset of therapy. Secondary endpoints include toxicity, QoL, functional and oncological outcomes. Data will be analysed separately for early (cN0) and early-intermediate (cN1) disease. The total planned sample size is 210 patients across the three arms. Interim analyses will be performed for each study arm to determine early failures and discontinue ineffective arms.

The trial was approved by the medical ethics committee NedMec of the Netherlands and is registered in the EU Clinical Trials Information System (CTIS). The results will be published in an international peer-reviewed journal.

CTIS EU 2024-514620-17-00

Deep vein thrombosis (DVT) in critically ill patients is often undetected. However, it is unclear whether ultrasound surveillance for early detection of DVT in high-risk medical-surgical intensive care unit (ICU) patients improves patients’ outcomes. The DETECT trial (Diagnosing deep-vein thrombosis early in critically ill patients) evaluates the effect of twice-weekly bilateral lower limb ultrasound compared to usual care on 90-day mortality of critically ill adult patients admitted to medical, surgical and trauma ICUs.

The DETECT trial is an international, parallel-group, open-label, randomised trial, which will recruit 1800 critically ill adults from over 14 hospitals in Saudi Arabia and Kuwait. Eligible patients will be allocated to twice-weekly bilateral lower limb ultrasound or usual care. The primary outcome is 90-day mortality. Secondary outcomes include lower limb proximal DVT, pulmonary embolism and clinically important bleeding. The first patient was enrolled on 21 March 2023. As of 8 April 2025, 711 patients have been enrolled from 14 centres in Saudi Arabia and Kuwait. The first interim analysis was conducted on 14 May 2025. We expect to complete recruitment by December 2026.

Institutional review boards (IRBs) of each participating institution approved the study. We plan to publish the results in peer-reviewed journals and present the findings at international critical care conferences.

Clinicaltrials.gov: NCT05112705, registered on 9-11-2021.

There is limited evidence on how to effectively treat individuals from marginalised populations with dependence on amphetamine and/or methamphetamine (collectively referred to hereafter as amphetamine dependence). The disease burden is extremely high in this population, especially related to psychiatric comorbidities, cardiovascular complications, injection-related infections and poor social functioning. ATLAS4Dependence is a multi-centre randomised, placebo-controlled, double-blind trial that will investigate the effectiveness and safety of substitution treatment with dextroamphetamine compared with placebo in people with amphetamine dependence.

The trial will recruit 226 adult patients in several outpatient clinics in Norway.Inclusion criteria comprise individuals with amphetamine dependence, defined as use on three or more days per week during the past 28 days, who currently inject or have formerly injected drugs. This includes individuals both with and without comorbid opioid dependence, as well as those currently receiving or not receiving opioid agonist treatment. Participants will be randomly assigned 1:1 to receive either dextroamphetamine or placebo for 12 weeks. Flexible doses within the range of 30–120 mg daily will be provided based on individual assessments. The participants in both arms will be offered standard psychosocial and medical follow-up in accordance with current clinical practice. The endpoint assessments will be conducted at 12 weeks with weekly self-reports and safety assessments and a follow-up assessment at 52 weeks. The primary objective of the study is to assess the impact of 12 weeks daily prescribed oral dextroamphetamine versus placebo on the use of illicit amphetamines as well as on the total amount of amphetamines used (including both illicit and prescribed sources). Secondary outcomes are the differences between the groups at 12 weeks regarding psychological distress, symptoms of psychosis, quality of life, cardiovascular risk factors, injection-related infections, executive functioning, attention-deficit hyperactivity disorder-related symptoms, sleep, violence risk, fatigue, symptoms of craving and withdrawal, treatment retention, days of use of illicit amphetamines and use at 4 weeks and 8 weeks during the intervention period, use of other illicit substances and alcohol, as well as a cost-effectiveness analysis (using private economy, criminal activity and health service utilisation) and a qualitative approach to assess overall experiences with the study intervention. Analysis and reporting will follow the Consolidated Standards of Reporting Trials guidelines. All tests will be two-sided. Descriptive results and the estimated effectiveness will be presented with 95% CIs. The difference between the groups at the primary time point (at the end of the 12-week trial) will be assessed using ² test (for use of illicit amphetamines measured by monthly urine tests) and Analysis of Covariance (ANCOVA) (for weekly self-reported total amount of amphetamines). Analyses for the primary endpoint will be undertaken on an intention-to-treat basis and reported on as such, but sensitivity analyses with per protocol analyses will also be presented.

The study is approved by European Medicines Agency, Clinical Trial Information System (CTIS). Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals.

CTIS 2023-510404-44-00.