Randomized Trials
RCT: Lack of significant effect of Paxlovid (nirmatrelvir–ritonavir) on symptom alleviation in Covid-19
26 Apr, 2024 | 11:49h | UTCStudy Design and Population:
This phase 2–3 randomized clinical trial investigated the efficacy of nirmatrelvir in combination with ritonavir for treating mild-to-moderate Covid-19 in adults. Participants, both vaccinated and unvaccinated, were enrolled based on their risk factors for severe Covid-19. The study included 1296 adults who had confirmed Covid-19 with symptom onset within the past 5 days. They were randomly assigned to receive either nirmatrelvir–ritonavir or placebo every 12 hours for 5 days.
Main Findings:
The primary endpoint was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Results showed that the median time to alleviation was 12 days for the treatment group and 13 days for the placebo group, a difference that was not statistically significant (P=0.60). Hospitalizations and deaths were slightly lower in the treatment group (0.8%) compared to the placebo group (1.6%), but this difference was also not statistically significant. Adverse events were similar across both groups, with dysgeusia and diarrhea being the most common in the treatment group.
Implications for Practice:
The findings indicate that nirmatrelvir–ritonavir treatment does not significantly reduce the time to symptom alleviation for Covid-19 compared to placebo among vaccinated or unvaccinated adults. These results suggest that further research is needed to explore the potential benefits of this treatment in specific subpopulations or in combination with other interventions.
Reference (free full-text):
RCT: Clarithromycin improves early clinical and inflammatory responses in hospitalized community-acquired pneumonia patients
23 Mar, 2024 | 20:25h | UTCStudy Design and Population: The ACCESS trial was a phase 3, prospective, double-blind, randomized controlled trial conducted in 18 Greek hospitals, involving adults hospitalized with community-acquired pneumonia who displayed systemic inflammatory response syndrome, had a Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin levels of 0.25 ng/mL or more. Participants were randomly assigned to receive either standard of care with intravenous cephalosporins or β-lactam/β-lactamase inhibitor combinations plus oral clarithromycin (500 mg twice daily for 7 days) or placebo. The trial aimed to evaluate the impact of clarithromycin on early clinical and inflammatory responses.
Main Findings: Among 278 participants allocated to clarithromycin (n=139) or placebo (n=139), the primary composite endpoint—indicating early clinical response and inflammatory burden reduction within 72 hours—was met by 68% of patients in the clarithromycin group compared to 38% in the placebo group, showcasing a significant difference (29.6%, odds ratio 3.40, p<0.0001). Serious treatment-emergent adverse events were slightly lower in the clarithromycin group than in the placebo group, although not statistically significant.
Implications for Practice: The addition of clarithromycin to the standard of care for hospitalized patients with community-acquired pneumonia significantly improves early clinical response and reduces inflammatory burden, potentially through modulation of the immune response. These results support the use of clarithromycin alongside β-lactam antibiotics in the treatment of community-acquired pneumonia, highlighting its role in enhancing patient outcomes by targeting early clinical and inflammatory indicators.
Reference
Prof Evangelos J Giamarellos-Bourboulis, MD et al. (2024). Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine, Volume(Issue), Pages. DOI: https://doi.org/10.1016/S2213-2600(23)00412-5. Access the study here: Link
RCT: No difference in ICU length of stay or 90-day mortality between tight and liberal glucose control
2 Oct, 2023 | 11:25h | UTCStudy Design and Population: This randomized controlled trial assessed the effects of tight versus liberal glucose control on the length of ICU stay in critically ill patients. A total of 9,230 patients were included, with 4,622 in the liberal-control group (insulin initiation when blood glucose levels exceeded 215 mg/dL) and 4,608 in the tight-control group (blood glucose targeted between 80 and 110 mg/dL). In both groups, parenteral nutrition was withheld during the first week of ICU admission. The primary endpoint was the duration of ICU stay, and 90-day mortality served as a key safety outcome.
Main Findings: No significant differences were observed in the primary endpoint, the length of ICU stay, between the two groups (hazard ratio 1.00; 95% CI, 0.96 to 1.04; P=0.94). The 90-day mortality rates were also similar (10.1% in the liberal-control group vs. 10.5% in the tight-control group, P=0.51). Incidences of severe hypoglycemia were low and statistically similar in both groups (1.0% in the tight-control group vs. 0.7% in the liberal-control group). Secondary outcomes, including new infections and the duration of respiratory and hemodynamic support, showed no significant differences. However, lower incidences of severe acute kidney injury and cholestatic liver dysfunction were observed in the tight-control group.
Implications & Limitations: The study supports existing evidence that tight glucose control doesn’t provide substantial benefits in reducing ICU stay duration or mortality. This suggests that a more liberal approach to glucose control may be preferable in most ICU settings, especially to minimize hypoglycemia risk. Key limitations of the study include its narrow focus on the absence of early parenteral nutrition, which could limit generalizability, and the inability to blind caregivers to treatment assignments. Future research should investigate the impact of tight glucose control in various patient subgroups and under different nutritional conditions.
RCT: Propafenone leads to quicker sinus rhythm restoration than amiodarone in supraventricular arrhythmias related to septic shock
1 Oct, 2023 | 15:19h | UTCStudy Design & Population: The research was a two-center, prospective, controlled parallel-group, double-blind trial involving 209 septic shock patients who had new-onset supraventricular arrhythmia and a left ventricular ejection fraction above 35%. Patients were randomized to receive either intravenous propafenone (70 mg bolus followed by 400–840 mg/24 h) or amiodarone (300 mg bolus followed by 600–1800 mg/24 h).
Main Findings: The primary outcomes focused on the proportion of patients in sinus rhythm 24 hours post-infusion, time to the first sinus rhythm restoration, and arrhythmia recurrence rates. No significant difference was observed in 24-hour sinus rhythm rates between the propafenone (72.8%) and amiodarone (67.3%) groups (p=0.4). Time to the first rhythm restoration was significantly shorter for the propafenone group (median 3.7 hours) compared to the amiodarone group (median 7.3 hours, p=0.02). Recurrence of arrhythmia was notably lower in the propafenone group (52%) than in the amiodarone group (76%, p<0.001). In the subgroup of patients with a dilated left atrium, amiodarone appeared to be more effective.
Implications & Limitations: The study suggests that while propafenone doesn’t offer better rhythm control at 24 hours compared to amiodarone, it does provide faster cardioversion and fewer arrhythmia recurrences, especially in patients with a non-dilated left atrium. No significant differences were observed in clinical outcomes, such as ICU or long-term mortality, between propafenone and amiodarone in the trial. Limitations include potential underpowering of the study and the inability to fully account for the impact of multiple covariates involved in the complex therapy of septic shock.
Commentary on Twitter:
Propafenone?70 mg bolus+ 400-840 mg/24h vs amiodarone?300 mg + by 600-1800 mg/24h for SVA in septic shock, RCT
?propafenone not better for rhythm control at 24h but excellent hemodynamic safety profile, cardioverting faster & fewer recurrences#FOAMCc
?https://t.co/GVuoxPD7Hy pic.twitter.com/rRlj00x71p— Intensive Care Medicine (@yourICM) September 13, 2023
RCT | Superior PFS with avelumab vs. chemotherapy in second-line treatment for mCRC with microsatellite instability
11 Aug, 2023 | 15:25h | UTCSee also: Visual Abstract
Commentary: Avelumab Outperforms Standard Second-Line Therapy in dMMR/MSI Metastatic CRC – Cancer Therapy Advisor
RCT | Field sobriety tests display insufficient accuracy for detecting THC-specific driving impairment
11 Aug, 2023 | 15:14h | UTCSee also: Visual Abstract
News Release: Can field sobriety tests identify drivers under the influence of cannabis? – University of California – San Diego
Commentary on Twitter
This randomized clinical trial investigates the accuracy of field sobriety tests administered by law enforcement officers to assess functional impairment and driving performance among individuals who have smoked cannabis. https://t.co/pThOOdZGUh
— JAMA Psychiatry (@JAMAPsych) August 2, 2023
[News Release] RCT | Semaglutide 2.4 mg reduces cardiovascular risk by 20% in adults with CVD & obesity
9 Aug, 2023 | 15:40h | UTCCommentaries:
SELECT: Semaglutide Cuts CV Events in Adults With Overweight or Obesity – TCTMD
Phase 2 RCT | Adding stereotactic body radiotherapy to immune checkpoint inhibitors fails to improve outcomes in solid tumor patients
9 Aug, 2023 | 15:28h | UTCCheckpoint Inhibitors in Combination With Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors: The CHEERS Phase 2 Randomized Clinical Trial – JAMA Oncology (link to abstract – $ for full-text)
See also: Visual Abstract
Commentary: Addition of SBRT to Immunotherapy in Advanced Solid Tumors – The ASCO Post
RCT | Exploring the impact of total pancreatectomy with islet autotransplantation to reduce postoperative complications
8 Aug, 2023 | 13:25h | UTC
Phase 2 Trials | Selective NaV1.8 inhibitor, VX-548, shows potential in acute postoperative pain management
7 Aug, 2023 | 14:51h | UTCSelective Inhibition of NaV1.8 with VX-548 for Acute Pain – New England Journal of Medicine (link to abstract – $ for full-text)
Video Summary: Selective Inhibition of NaV1.8 for Acute Pain | NEJM
Commentaries:
High-Dose VX-548 Reduces Acute Pain Post-Surgery – HCP Live
High-Dose VX-548 Reduces Acute Pain Over 48 Hours – HealthDay
Commentary on Twitter
Original Article: Selective Inhibition of NaV1.8 with VX-548 for Acute Pain https://t.co/ogmEx6FNKo#surgery pic.twitter.com/0FpipA1xey
— NEJM (@NEJM) August 5, 2023
RCT | Upfront radiosurgery reduces tumor volume vs. a wait-and-scan approach in small- to medium-sized vestibular schwannoma
7 Aug, 2023 | 14:40h | UTCUpfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial – JAMA (free for a limited period)
See also: Visual Abstract
Commentary on Twitter
Among patients with small or medium vestibular schwannoma, a treatment strategy consisting of upfront radiosurgery was more effective at reducing tumor volume at 4 years than was the initial wait-and-scan approach. https://t.co/Qv3YZVsq2Q pic.twitter.com/aNeu7MJfl0
— JAMA (@JAMA_current) August 2, 2023
RCT | Zolbetuximab plus CAPOX as potential first-line treatment for CLDN18.2+, HER2- advanced gastric adenocarcinoma
7 Aug, 2023 | 14:38h | UTC
Commentary on Twitter
In the phase 3 GLOW trial, CAPOX plus zolbetuximab significantly improved progression free survival and overall survival in patients with CLDN18.2+, HER2- untreated #GastricCancer or gastroesophageal junction adenocarcinoma @AstellasUS @mdmanishshah https://t.co/YYbLHhiyOq
— Nature Medicine (@NatureMedicine) August 1, 2023
RCT | 52-week antidepressant adjunctive therapy did not lead to a statistically significant benefit over 8-week therapy in bipolar I depression
4 Aug, 2023 | 12:11h | UTCDuration of Adjunctive Antidepressant Maintenance in Bipolar I Depression – New England Journal of Medicine (link to abstract – $ for full-text)
News Release: Modern antidepressants may reduce risk of relapse for patients with bipolar depression – University of British Columbia
Commentary on Twitter
Among patients with bipolar I disorder who had remission of depression, there was no significant difference in the incidence of relapse of any mood episode between 8 weeks and 52 weeks of antidepressant treatment. Full results of the BEAM-BD trial: https://t.co/rCkCqIfMb6
— NEJM (@NEJM) August 2, 2023
Review | ‘Pragmatic’ trials changing research: Balancing traditional controls with real-world care needs
4 Aug, 2023 | 12:08h | UTCClinical Trials Overview: From Explanatory to Pragmatic Clinical Trials – Mayo Clinic Proceedings
RCT – 2ry analysis | Use of NIPPV, NHFOV post-extubation outperforms NCPAP in neonates with severe respiratory failure or extremely preterm
4 Aug, 2023 | 11:48h | UTC
Commentary on Twitter
2nd analysis of NASONE trial in @JAMANetworkOpen examines whether NHFOV is superior in reducing the duration of IMV in comparison to NIPPV and NCPAP in infants born < 28 weeks https://t.co/oWqvO4E5QF
2022 NASONE study: https://t.co/1rfZpaIseN #EBNEOalerts #neoEBM #neotwitter pic.twitter.com/w3Au8s62K7
— Evidence-Based Neo (@EBNEO) July 5, 2023
RCT | Recombinant human prourokinase demonstrates noninferiority to alteplase in acute ischemic stroke treatment
3 Aug, 2023 | 13:46h | UTCSee also: Visual Abstract
RCT – 2ry analysis | Omega-3 supplementation linked to increased AF risk in post-MI patients
3 Aug, 2023 | 13:45h | UTCRelated:
M-A: Omega-3 fatty acids supplementation is associated with increased risk of atrial fibrillation.
Commentary from the author on Twitter (thread – click for more)
RCT data consistently show that Omega-3 suppl increase AF risk https://t.co/LQVHfPNtKL
In this substudy of the #OMEMI trial we add novel data from thumb-ECG screening and serum EPA/DHA, supporting a causal relation between omega-3 (EPA) and AF!https://t.co/B9VoDNQpZi
? 1/4 pic.twitter.com/GFYGfVaNMq
— Peder L. Myhre ? (@pmyhre) July 28, 2023
RCT | Ferric derisomaltose plus tranexamic acid may reduce blood transfusion risk by 50% in hip surgery
3 Aug, 2023 | 13:18h | UTCFerric derisomaltose and tranexamic acid, combined or alone, for reducing blood transfusion in patients with hip fracture (the HiFIT trial): a multicentre, 2 × 2 factorial, randomised, double-blind, controlled trial – The Lancet Haematology (link to abstract – $ for full-text)
RCT | No significant recurrence-free survival improvement with everolimus post-renal carcinoma surgery
3 Aug, 2023 | 13:17h | UTCAdjuvant everolimus after surgery for renal cell carcinoma (EVEREST): a double-blind, placebo-controlled, randomised, phase 3 trial – The Lancet (link to abstract – $ for full-text)
RCT | Early oral antibiotic switch in low-risk neutropenic sepsis shows mixed results
3 Aug, 2023 | 13:15h | UTC
Perspective | The most important trial in modern cardiology (Critical appraisal of the ISCHEMIA trial)
2 Aug, 2023 | 14:11h | UTCChapter 3: The Most Important Trial in Modern Cardiology – Sensible Medicine
See also:
Chapter 1: What Does it Mean to Discover a Coronary Blockage? – By Dr John Mandrola
Chapter 2: On the meaning of a coronary blockage – By Dr John Mandrola
Related/Original Articles:
ISCHEMIA Trial: Initial Invasive vs. Conservative Strategy for Stable Coronary Disease
ISCHEMIA Trial: Management of Coronary Disease in Patients with Advanced Kidney Disease
RCT | Multiple sclerosis disease-modifying therapy continuation versus discontinuation in older individuals
2 Aug, 2023 | 14:00h | UTCRisk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial – The Lancet Neurology (link to abstract – $ for full-text)
Commentaries:
Discontinuing Multiple Sclerosis Therapies at Age 55 or Older – NEJM Journal Watch
RCT | Atogepant outperforms placebo in reducing migraines over 12 weeks
2 Aug, 2023 | 13:56h | UTCAtogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial – The Lancet (link to abstract – $ for full-text)
RCT | Lazertinib offers 20.6-month of median PFS in EGFR-mutated NSCLC vs 9.7 months with gefitinib
2 Aug, 2023 | 13:55h | UTC
RCT | Maternal egg intake in early neonatal period does not impact infant egg allergy risk
2 Aug, 2023 | 13:47h | UTCSee also: Visual Abstract
