Every year the Clinical Trials Distance Learning Programme a joins celebrations of International Clinical Trials Day on May 20^th with a focus on an important trial linked to LSHTM and its mission. This year the programme showcases the work of the Tight K Trial.

Tight K is a collaboration between the LSHTM Clinical Trials Unit and a number of clinical centres in Germany. It was designed to find out whether giving extra potassium to patients after coronary artery bypass (CABG) surgery is necessary.  Read more about the trial design, implementation, data collection and analysis, and explore options for the study of clinical trials at LSHTM: Celebrating International Clinical Trials Day 2025

Dr. Amy Brenner from the LSHTM CTU is quoted in this article in The Guardian describing the underrepresentation of women in UK medical trials.  Amy explains why the lack of women-specific data matters and describes how we design inclusion into our trials through patient and public involvement. 

Transcatheter Aortic Valve Implantation is a procedure used to treat aortic stenosis, a condition where the aortic valve becomes narrow and stiff. During a TAVI procedure, debris from the blood vessels and heart valve is often released into the bloodstream. This debris can block the arteries which supply the brain, and cause a stroke.

Cerebral embolic protection (CEP) devices act like a small filter, and have been proven to capture debris before it reaches the brain. The Sentinel device is a CEP device manufactured by Boston Scientific and is approved for use in Europe and USA.

The BHF PROTECT-TAVI trial was a large-scale randomised controlled trial conducted across 33 UK centres between 2020 and 2024. It evaluated whether the routine use of the Sentinel CEP device reduces stroke risk in patients undergoing TAVI. 7635 patients were randomised either to TAVI with the Sentinel CEP device (CEP groups) or to TAVI without the CEP (Control group).

The primary outcome – stroke within 72 hours of randomisation or by discharge from hospital if sooner – occurred in 2.1% of the CEP group and 2.2% of the control group, showing no evidence of reduced incidence of stroke attributable to the use of the CEP device. Additionally, similar results were seen between the treatment groups in the occurrence of all-cause mortality (0.8% vs. 0.7%) and disabling stroke (1.2% vs. 1.4%).

Based on the results of the trial, there is no evidence to support a recommendation for routine use of CEP in TAVI. An individual patient-level meta-analysis in over 10,000 participants is planned with the PROTECTED TAVR trial (n=3000).

The primary results of the BHF PROTECT-TAVI trial, which were presented at the American College of Cardiology conference on 30th March, have been published in the New England Journal of Medicine and can be found here.

The trial was funded by British Heart Foundation and Boston Scientific. Oxford University sponsored the trial. 

The Medical Statistics Department (MSD) at the London School of Hygiene and Tropical Medicine (LSHTM) will be running a short course on the essentials of Clinical trials from 7- 11 July 2025. This course has been run in London since 1991. The course is taught by members of the Department of Medical Statistics who have extensive experience in the design, conduct and analysis of trials in a variety of clinical specialities. This unique 5-day course is designed to give attendees a clear understanding of the fundamental principles of Randomised Clinical Trials (RCTs). The course will have a hybrid format and participants can choose to attend in person in London or Online. For further information and an application form please visit the LSHTM Webpage. 

Read about the latest findings from the WOMAN trials published in two papers in The Lancet in October 2025

A highly successful 2^nd LSHTM Trials Day was held on Monday 4^th November in Entebbe, Uganda, and online.  Read about the event here.

Results from the TIGHT K Trial, a major medical research trial run by the LSHTM Clinical Trials Unit, were presented for the first time at the European Society of Cardiology Congress (ESC) in London, UK, on Saturday 31^st August 2024 and simultaneously published in the renowned Journal of the American Medical Association.

Atrial fibrillation, an abnormal heart rhythm, occurs in 1 in 3 patients after coronary artery bypass graft heart surgery. Many treatment centres give extra potassium to keep blood concentrations high in order to prevent it- a practice which is expensive. However, it wasn’t known whether this works. The TIGHT K Trial was funded by the British Heart Foundation to find out.

A total of 1690 patients from 23 centres in the UK and Germany were randomised to receive extra potassium when blood levels dropped into the top end of the ‘normal range’, or to receive it when levels dropped below the bottom end of normal.

The study found that the risk of atrial fibrillation was no greater when lower potassium concentrations were targeted.

Professor Ben O’Brien from the Berlin Heart Institute, who presented the findings at the ESC Congress, said, “We learned that the group who had fewer doses of potassium got the same amount of heart rhythm problems as the group who got more doses. When patients got less potassium, it saved money (£87 per patient). Potassium supplementation is also associated with other risks and can be unpleasant for patients to receive. Our results indicate that it is now time to abandon the widespread practice of maintaining high-normal potassium levels after coronary artery bypass grafting”.

The manuscript in the Journal of the American Medical Association can be found here. 

Listen here for an interview with Professor Benjamin O’Brien on the American College of Cardiology podcast ACCEL LITE discussing the results of the Tight K Trial

The tranexamic acid (TXA) trials, run by the Clinical Trials Unit at the London School of Hygiene & Tropical Medicine, have featured in the CaSE July briefing. CaSE, the Campaign for Science and Engineering, is the UK’s leading independent advocate for science and engineering. The TXA case study highlights two large scale trials looking at TXA for trauma and maternal health and the global impacts of these trials, highlighting the crucial role that universities play in the research and development ecosystem.

Explore the briefing to find out more

Evidence from the OMWaNA trial shows that kangaroo mother care (KMC) initiated before clinical stabilisation did not reduce early neonatal mortality but had other clinical benefits and was cost effective relative to incubator care. Findings from OMWaNA are published in the Lancet

The OMWaNA trial recruited 2,221 neonates across five hospital in Uganda between 2019 and 2023, aiming to assess the effectiveness, safety, costs and cost effectiveness of KMC initiated before clinical stabilisation when compared to standard care in neonates weighing up to 2000g. The study was led by researchers from the London School of Hygiene and Tropical Medicine and the Medical Research Council/Uganda Virus Research Institute (MRC/UKVI)

You can view the global webinar held to coincide with the publication of results, featuring presentations by the trial team, an interview with a trial participant, and a panel discussion with global health experts and policy makers here, and a blog describing experiences from the trial can be found here.

In an expert opinion piece; Richard Evans, Senior Manager of the LSHTM Clinical Trials Unit discusses the need to improve the representation of women at all stages in the design and implementation of cardiovascular trials.  This builds on a recently published article in Nature Reviews Cardiology.

Women are underrepresented at all levels in cardiovascular trials including participants, clinicians and researchers. This leads to, and results from, inequities in healthcare with cardiovascular disease being underdiagnosed and undertreated in women. Members of the cardiovascular trials team at the London-based LSHTM Clinical Trials Unit have contributed to an article recently published in Nature Reviews Cardiology. The article sets out steps for addressing sex-based inequities in cardiovascular clinical trials.  Read more about the work here. 

The Medical Statistics Department (MSD) at the London School of Hygiene and Tropical Medicine (LSHTM) will be running a short course on the essentials of clinical trials from 1-5 July 2024. The course is relevant to those who are keen to gain an understanding of the rigorous evaluation of interventions in health care, including clinical research professionals, research managers, and other scientists with an interest in clinical trials. The course will be delivered using a hybrid format with students able to attend either in person at LSHTM or online. To find out more information and apply, please visit the LSHTM webpage. 

The Directors of the London-based LSHTM Clinical Trials Unit (CTU) were hosted by colleagues at MRC/UVRI & LSHTM Uganda Research Unit from 6^th-9^th February 2024. The purpose of the visit was to strengthen collaboration on randomized controlled trials. It came at an opportune time as the Uganda unit is in the process of consolidating and extending its clinical trials capability under a new Clinical Trials and Research Platform.  Read more about the visit on the Trials Network webpages 

The Trials Network is running a series of six seminars through 2024 on Practical Issues in Clinical Trials.  The seminars are open to all and will be run as online webinars.

The seminar series will feature speakers from across LSHTM and our research partners.  Each seminar will include a brief overview of current practice, theory and evidence, followed by worked examples from different presenters.

• Seminar 1: Practical Issues in Clinical Trials seminar 1: PPIE and Community Involvement, Tuesday 6 February 1-2 pm GMT (Zoom webinar)

In the first seminar, Professor Caroline Free, co-director of the LSHTM Clinical Trials Unit, Dr Armel Zemsi, Head of the Clinical Trials Unit at the MRC Unit The Gambia at LSHTM and colleagues from the MRC/UVRI & LSHTM Uganda Research Unit will present on the state of current evidence and practice around patient and community involvement in research, and share concrete examples from their respective regions in order to provide an overview on what works and the lessons learned.

Future seminars in the series:

• 9 April 2024 : Starting a trial/logistics
• 4 June 2024 : Running a trial - Part 1: Protocol compliance, monitoring
• 3 September 2024: Running a trial - Part 2: Recruitment and follow up
• 5 November 2024: Running a trial - Part 3: Data and Safety Monitoring Board (DSMB) options

28 January 2025: Closing down a trial and dissemination: Publication, including PPI in dissemination, media. 

The final results of TB-PRACTECAL have been published in The Lancet Respiratory Medicine:

• Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): an open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial

TB PRACTECAL is a phase 2/3 multicentre, randomised, controlled clinical trial to find short, tolerable and effective treatments for people with drug-resistant tuberculosis (DR-TB). The trial evaluated the efficacy and safety of three 24-week, all-oral regimens for the treatment of rifampin-resistant TB. These results confirm the interim results published in the New England Journal of Medicine in 2022:

• A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis 

A paper published in the Journal of Thrombosis and Haemostasis, by researchers from Semmelweis University in Hungary and the CTU reveals that anaemia can hinder blood clotting and potentially make tranexamic acid (TXA), a drug used to prevent postpartum haemorrhage (PPH) in women, less effective.

This study was conducted to determine the separate and combined role of TXA and red blood cells in the inhibition of fibrinolysis. Read the publication: 

• Synergism of red blood cells and tranexamic acid in the inhibition of fibrinolysis
   

The WOMAN-2 trial is assessing whether giving TXA can prevent PPH in women with moderate and severe anaemia. The results of this trial are expected in 2024. 

Important new results and health economic analysis from REVIVED-BCIS2 have been published.

A secondary analysis was published in JAMA cardiology:

• Viability and Outcomes With Revascularization or Medical Therapy in Ischemic Ventricular Dysfunction A Prespecified Secondary Analysis of the REVIVED-BCIS2 Trial 

These results were presented at the American College of Cardiology conference (ACC 2023) and revealed that percutaneous coronary intervention (PCI) remained ineffective, regardless of the extent of viability. In addition, the analysis showed that measuring scar burden is major predictor of events and left ventricular recovery.

A health economic analysis of data from REVIVED-BCIS2 was published in AHA Journals:

• Percutaneous Revascularisation for Ischemic Left Ventricular Dysfunction: Cost-Effectiveness Analysis of the REVIVED-BCIS2 Trial 

These results were presented at the American Heart Association conference (AHA 2023). This analysis showed that PCI was associated with minimal difference in QALYs and considerable incremental cost and that a strategy of PCI for ischemic left ventricular systolic dysfunction (ILVD) is not a justifiable use of healthcare resource.

The qualitative results of the Safetxt trial have been published in BMJ open: A qualitative study exploring experiences of the safetxt digital health intervention to reduce sexually transmitted infections in young people in the UK 

Safetxt was a single blind randomised controlled trial and a linked qualitative study to establish the effectiveness of a safer sex intervention delivered by mobile phone messaging on STI infection. 

For more details listen to the STIRIG series event.

The LSHTM Trials Network is holding an inaugural Trials Day as a hybrid event at Mary Ward House on Monday 6 November 2023. The day will showcase a selection of LSHTM’s vast experience and innovation in randomised controlled trials and there's a great line-up of speakers including keynotes by CTU members Eni Balogun on tranexamic acid trials and Richard Evans on cardiovascular trials

See the full agenda.

The WOMAN-2 trial has achieved its target of recruiting 15,000 women randomised across sites in Nigeria, Pakistan, Tanzania and Zambia. 

The trial's aim is to see if giving tranexamic acid can prevent postpartum haemorrhage (PPH) and other severe outcomes in women with moderate and severe anaemia. Find out more about the trial.
 

The ARREST trial, involving the London Ambulance Service and all hospitals in London, found there’s no difference in 30-day survival for out-of-hospital cardiac arrest (OHCA) patients who were taken by ambulance to a specialist cardiac arrest centre compared with those delivered to the geographically closest emergency department. The study also found no overall difference in brain and nerve function at discharge and no difference between the two groups in death rates after three months.

The results were presented at the European Society of Cardiology Congress and published in The Lancet:

• Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial
• Supplementary appendix (pdf)

The trial’s aim was to determine the best post-resuscitation care pathway for patients without ST-segment elevation (STE). The ARREST trial involved 862 patients recruited across London between 2018 and 2022.

Read about the pilot:

• A Randomised tRial of Expedited transfer to a cardiac arrest centre for non-ST elevation ventricular fibrillation out-of-hospital cardiac arrest: The ARREST pilot randomised trial

Further analysis from the REVIVED-BCIS2 trial shows:

• Percutaneous coronary intervention (PCI) does not reduce death or aborted sudden death in ischemic left ventricular dysfunction
• There’s no difference in the rate of implantable cardioverter defibrillator (ICD) therapies or sustained ventricular arrhythmias

Read the recent publication: Arrhythmia and Death Following Percutaneous Revascularization in Ischemic Left Ventricular Dysfunction: Prespecified Analyses From the REVIVED-BCIS2 Trial

REVIVED-BCIS2 evaluated the efficacy and safety of PCI compared to optimal medical therapy (OMT) alone for ischaemic left ventricular dysfunction. Seven hundred patients were enrolled across 40 centres in the UK between August 2013 and March 2020.

See the main trial results in the New England Journal of Medicine: Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction

Evidence from the WOMAN-2 trial shows that pregnant women with anaemia are substantially more likely to suffer life-threatening bleeding after childbirth. These findings are published in the The Lancet Global Health:

• Maternal anaemia and the risk of postpartum haemorrhage: a cohort analysis of data from the WOMAN-2 trial

For further information listen to this podcast of Prof Rizwana Chaudhri and Prof Ian Roberts discussing their research investigating the association between maternal anaemia and post-partum haemorrhage from The Lancet Global Health.

Watch this video on: How maternal anaemia causes severe bleeding in childbirth

The WOMAN-2 trial recruited 10, 620 women with anaemia from hospitals in Nigeria, Pakistan, Tanzania and Zambia between August 2019 and November 2022. WOMAN-2 examined the association between anaemia and the risk of postpartum haemorrhage (PPH). The trial looks at whether giving tranexamic acid can prevent PPH and other severe outcomes in women with moderate and severe anaemia.

Read more about the WOMAN-2 trial here.