Surgical Trials

CLARITY is a cluster-randomised trial of a surgical education package to improve patient care in right iliac fossa pain. The trial will be jointly delivered by the West Midlands Research Collaborative (WMRC) and STARSurg. We have launched CLARITY at ten pilot sites in the UK and aim to enter the main phase of the trial in the UK and Republic of Ireland in September 2024.

In the complex world of vascular surgery, where “high risk” is basically our love language, one topic continues to spark the debate: the uncomplicated type B aortic dissection. “Uncomplicated” may sound reassuring, but don’t be fooled. In reality, “uncomplicated” may just mean not yet complicating your life. These patients represent the calm before the storm, leaving clinicians to weigh whether it’s better to follow a conservative approach or go in early and do something heroic (and preferably endovascular).

Once upon a time, all type B dissections were approached as ticking time bombs — open surgery, big incisions and lots of drama. Outcomes, however, were far from ideal. As evidence emerged that doing less often yielded better results, the field shifted direction. Medical therapy became the dominant approach; enter the era of “let’s control the blood pressure and hope for the best.” Today, medical therapy — mainly antihypertensives and analgesics — remains the cornerstone for managing uncomplicated type B dissections.

Short-term survival left everyone quite satisfied: in-hospital survival was about 90%. Long-term results, however, were less pleasing. Survival drops to around 79% at five years, with approximately one-third of these initially “uncomplicated” patients eventually requiring intervention – procedures that are technically more challenging in the chronic phase with higher procedural risks. Turns out, “uncomplicated” is more complicated than it sounds.

PROTECT is a national platform trial designed to deliver multiple multi-centre randomised and non-randomised comparisons in adult surgical patients. Individual trial components will span phase II to phase IV, depending on the specific research question.

The study will be conducted across NHS surgical services and will include patients aged 18 years and over undergoing care within an NHS surgical pathway.

Locally advanced rectal cancer involves multimodality treatment that combines 5-fluorouracil (5-FU) based chemotherapy, chemoradiation and surgical resection. Total neoadjuvant therapy and radiation (TNT) has shown to induce complete tumor regression in up to 30-40% of patients1 and is associated with improved disease free survival.2 Furthermore, patients who attain a complete response to TNT, may be eligible for organ preserving strategies, offering them the potential to avoid radical resection and its attendant morbidity, including possible low anterior resection syndrome, bowel dysfunction, or permanent stoma formation.2-5 Despite its benefits, response to TNT remains markedly heterogeneous with more than half of patients not attaining a complete clinical response.6 The biological determinants underlying this variability remain an area many researchers are working to define. Identifying mechanisms that underlie variable treatment responses may enable novel strategies to enhance tumor regression and expand organ-preservation opportunities.

Emerging data from our group and others has suggested that the intertumoral microbiome may influence the variability in treatment response.7-9 Anaerobic bacteria, particularly Fusobacterium nucleatum8,10, have been associated with resistance to TNT and poor pathologic regression.11 Importantly, the intratumoral microbiome has shown to be dynamic9,12 and can be influenced by variables such as stress, diet, and therapies.13 Models have demonstrated that exposure to agents such as 5-FU or metronidazole can eradicate fusobacterium nucleatum and when eradicated patients had improved outcome.11,12,14,15

Building on these observations, we developed a phase II clinical trial to quantify intratumoral bacterial populations, particularly anaerobes and evaluate the impact of metronidazole administration on these tumoral bacterial populations. Metronidazole, an imidazole antibiotic, acts as a prodrug that is activated under anaerobic conditions, disrupts bacterial DNA synthesis ad metabolism.16,17 This trial aims to determine if selective depletion of anaerobes can be enhanced by the administration of metronidazole.

“They’re called ‘trials’ for a reason” a very experienced clinical academic once told me during a difficult oversight meeting for a study I was leading. This randomised controlled trial (RCT) of an intervention used during emergency bowel surgery was struggling with recruitment rates after the pandemic and we were discussing ways to get things back on track. With some intensive efforts from all involved – and a fair amount of stress - we did manage to finish participant recruitment. Unperturbed, I even took on co-leadership of another emergency perioperative trial, CAMELOT, exploring rectus sheath catheter infusions for post-laparotomy analgesia.

Many of those interested in research and quality improvement for patients undergoing emergency surgery have felt compelled by the obvious health burden: 30,000 emergency laparotomy cases each year in the UK, with a 10% mortality rate at one month after surgery. The latter seems to have stubbornly plateaued after an initial improvement soon after our national audit rolled out. Yet most perioperative research is still directed at those undergoing elective surgery, with much lower overall risks. This is clearly a patient group that remains under-served, and with a lot to gain from even small improvements in postoperative outcomes. But formally evaluating new treatments in this setting is not without challenge.

The IMPROVE-AD study is funded by the National Heart, Lung, and Blood Institute in the US. The study aims to understand how best to treat type B aortic dissection. It will include up to 1,100 patients from 60 hospitals across the United States and Canada. The trial is powered to demonstrate whether upfront thoracic endovascular repair (TEVAR) is superior to the standard of care of Medical Therapy and intervention when needed during follow up over 4 years. The entire study duration is 7 years with a planned completion in 2030.

In the UK, around 5,000 major lower limb amputations (MLLA) occur every year, meaning that every 2 hours, someone in the UK has a leg removed and their life is changed forever. This number is increasing due to the ageing population and rising prevalence of diabetes. The care of these patients costs the NHS approximately £200 million a year, not including costs associated with formal and informal care, homecare visits and residential or nursing home placement. Following MLLA many patients do not return to independent living, with approximately one third being discharged to a care facility. MLLA also leads to substantial health implications, including anxiety, depression, altered body image and social discomfort, and the loss of general fitness and independence, which all contribute further to patient burden and healthcare costs.

MLLA includes below knee amputations (BKA), above knee amputations (AKA) and through knee amputations (TKA). Irrespective of the level of amputation, a MLLA has a significant impact on quality of life, though this can be mitigated. A recent review found that the ability to walk successfully with a prosthetic limb following MLLA, something more difficult with an AKA, had the greatest positive impact on quality of life. Accordingly, a BKA to preserve the knee joint, and thus maximise potential to utilise a prosthesis, is performed in preference to higher levels of amputation wherever possible. Patients not suitable for a BKA are usually offered an AKA, and less commonly a TKA as an alternative. Compared to an AKA, a TKA may result in superior outcomes via improved rehabilitation, easier control of an artificial leg and/or balance in a wheelchair. However, a TKA can also result in wound healing complications. Patients report positive and negative experiences with both AKA and TKA.

When a BKA is not suitable, both AKA and TKA surgeries are used in clinical practice. TKA is rarely used in the UK (less than 2% of MLLA) though may confer benefits as above, however, high-quality research to provide evidence to clearly define which amputation method results in the best outcomes for patients is lacking.

Knee osteoarthritis is one of the most common musculoskeletal conditions, affecting almost one in five people over the age of 45 in the UK — around 4 million people. For many, it means living with chronic pain, limited mobility, and a gradual decline in quality of life. At its most severe, the only effective option is knee replacement surgery.

But what about those who aren’t yet at that stage? Despite trying physiotherapy, anti-inflammatories, and combinations of painkillers, many patients remain stuck in a treatment gap. Their pain is poorly controlled, yet surgery is not an option.

A new approach — genicular artery embolisation (GAE) — might offer hope. The procedure blocks small blood vessels around the knee that are thought to drive inflammation and pain. Early studies have hinted at benefit, but the evidence so far is mixed: one small trial showed no improvement, while another found a modest reduction in pain. Despite this uncertainty, the technique is already being used internationally.

Superficial venous intervention has transformed the treatment of varicose veins, offering patients minimally invasive solutions with excellent short-term outcomes. Yet, despite technical advances, an important question remains unresolved: Should pharmacological thromboprophylaxis be routinely prescribed to prevent postoperative deep vein thrombosis (DVT)?

The THRIVE trial (THRomboprophylaxis In superficial endovenous interVEntion) is the first randomised controlled study designed to address this uncertainty.1 By generating robust clinical evidence, THRIVE has the potential to influence international practice and shape future guideline recommendations.

Varicose veins are common, affecting up to 45% of the UK population and are associated with reduced physical and mental health-related quality of life.2,3 Symptomatic varicose veins are now routinely treated with endovenous thermal ablation, non-thermal ablation or mechanochemical techniques.4 While effective, these procedures carry a recognised risk of venous thromboembolism (VTE).

The NEON (Nerve rEpair Or Not) trial is a randomized controlled trial investigating whether microsurgical suture repair provides benefits over simple nerve alignment for digital nerve injuries—one of the most common nerve injuries requiring surgical treatment.1 Digital nerve injuries affect approximately 3,000 patients annually in the UK, typically caused by sharp lacerations to fingers.2 Standard treatment involves specialist referral and direct suture repair under microscope magnification. However, prior to NEON, no randomized trials had compared suture repair to non-repair approaches, with existing evidence limited to small, biased observational studies.3

This multicentre trial randomized 122 adult patients with suspected unilateral digital nerve injuries across 17 NHS hospitals. After surgical exploration confirmed nerve division, participants were randomized 1:1 to either:

Microsurgical suture repair: Nerve ends aligned and sutured under magnification