Pre hospital phase clinical trials Rutger van der Pijl
Photo courtesy of Rutger van der Pijl | Registered Ambulance Nurse, Ambulance IJsselland

Ambulance studies are on the rise. Globally, cardiologists, funders and CROs are coming together to perform pre-hospital phase trials with one main goal: to advance the commencement of treatment, before patients reach the hospital. Because those early minutes are crucial.

We’re talking to Prof. Arnoud van ‘t Hof, M.D., Ph.D., FESC, Head of the Department of Interventional Cardiology in the MUMC, Maastricht and the Zuyderland MC in Heerlen, The Netherlands. He’s been playing a key role in Diagram’s ambulance studies and is the Principal Investigator of the current CELEBRATE trial. 

Prof. Van ‘t Hof talks to us about the pivotal role of the ambulance, the need to optimise the care chain and why he believes that The Netherlands has a unique role to play in pre-hospital phase trials.

Pre hospital phase trials Prof Arnoud van t Hof

Shaping Interventional Cardiology

Diagram and Prof. Van ‘t Hof have been working together for over 20 years, improving health care by solid scientific cardiovascular research.

As an interventional cardiologist at the Isala Hospital in Zwolle, our birthplace, Prof. Van ’t Hof focused his research on myocardial infarction treatment. In 2017 he took his expertise to the southern part of the Netherlands, to further shape interventional cardiology in this region of the country.  

Why Researching Pre-Hospital Phase?

The future of myocardial infarction treatment is centred in the ambulance.

Throughout his career, Prof. Van ‘t Hof has been especially interested in researching the pre-hospital phase, the time between the start of symptoms and arrival at a hospital. Why?

“Because the future of myocardial infarction treatment is centred in the ambulance,” he says.

According to Prof. Van ‘t Hof, Dutch people are well educated when it comes to recognising a heart attack. We immediately call 112 when experiencing suspicious symptoms, like chest pain. “And in those cases, the [land or air] ambulance will be the first one present,” he says.

“At the time the ambulance arrives, patients have been experiencing complaints for 15-20 minutes only. And if the ambulance staff is able to diagnose and start treatment directly on the spot, then you drastically improve the chances of a positive outcome. Because with myocardial infarctions those early minutes are crucial.”

The ambulance is the right vehicle; at the right location with the right people to start treatment immediately.

A myocardial infarction occurs when one or more areas of the heart muscle don’t get enough oxygen, because the blood supply to the heart is suddenly blocked. The coronary arteries need to be opened as quickly as possible. Prof. Van ‘t Hof: “If you start treatment two hours later, you’re too late, the damage has been done. Especially in remote areas and countries with long driving distances for ambulances, you miss the opportunity to adequately help your patient.

That’s why the ambulance is the right vehicle; at the right location with the right people to start treatment immediately,” Prof. Van ‘t Hof concludes.

“On top of starting the treatment as early as possible, it’s also about risk assessment,” Prof. Van ‘t Hof adds. He explains that you could already perform triage in the ambulance, separating high-risk from low-risk patients, and then take actions accordingly.

“For example, with high-risk patients the emergency services personnel can already announce arrival at the angioplasty centre [dottercentrum], so they can prep the cath lab to receive patients immediately upon arrival, without losing valuable time.”

Major steps in Pre-Hospital Phase Studies

Twenty years ago, the first ambulance studies with heart attack patients were performed. Since then, they’ve evolved rapidly, with the current CELEBRATE study being the largest. Prof. Van ‘t Hof gives us an overview of the major achievements in the pre-hospital research landscape.

STEP 1: Diagnostics

Moving diagnostics from the hospital to the ambulance has been one of the greatest breakthroughs.

Prof. Van ‘t Hof shares: “We started our ambulance studies with myocardial infarction patients in the late nineties, initially to improve diagnostics. The main goal was to record an ECG (electrocardiogram) in the ambulance and to be able to read this ECG [using the available algorithm].”  

Diagram is closely involved in the development of novel tools to improve adequate diagnosis of coronary ischemia in the ambulance using digital ECG and point of care testing.

“The second goal was to take appropriate action based on this reading,” Prof. Van ‘t Hof continues. He explains: “For example, when diagnosing a clear myocardial infarction, that you decide to drive directly to the angioplasty centre instead of the nearest hospital.

These studies resulted in an incredible logistical improvement in the treatment of myocardial infarction,because patients arrive faster at the right location for proper treatment.

Today, almost 20 years later, I still believe this to be one of the greatest breakthroughs: by moving diagnostics from the hospital to the ambulance, you drastically improve chances of a positive outcome.”

STEP 2: Treatment

Prof. Van ‘t Hof continues: “In later studies, we developed this further. On top of performing diagnostics, we also wanted to be able to start treatment where possible. For example, by administering blood thinning medication to open up the arteries while en route to the hospital.  

In 2008, we researched this with On-Time 2, a successful ambulance trial that we rolled out across The Netherlands, Germany and Belgium. The impressive results put The Netherlands, and Diagram, on the map; it showed the world our expertise and experience in pre-hospital phase trials.”

When asked why The Netherlands is so experienced with this type of trial, Prof. Van ‘t Hof shares it’s because of our unique infrastructure. Here in The Netherlands, unlike most other countries, the ambulances are staffed by highly educated people with a medical background and the legal authority to take action. “Apart from some other European countries like Spain, Denmark and Czech Republic, it’s an infrastructure you can’t find anywhere else in the world,” he explains.

STEP 3: Triage

Triage is the third big breakthrough: the care has now been expanded to different patient groups.

After diagnostics and treatment, ten years ago another major step was achieved: triage.

Prof. Van ‘t Hof: “I started researching myocardial infarction, but it expanded to patients who were experiencing suspicious symptoms, but weren’t showing clear markers for infarction.

Because 95% of people calling 112 with chest pain are actually not having a heart attack. Having to transport all those people urgently to the heart centres, puts too much pressure on the health care system. It costs money, time and manpower to separate high-risk patients from patients who are experiencing muscle ache or stress. This instigated the idea to perform triage already in the ambulance.”

Triage separates patients according to how urgent they need care. The triage result influences the order and priority of emergency treatment, the order and priority of emergency transport and/or the patient’s destination.

“So, ten years ago, we expanded our research to a different patient group: people who were experiencing chest pain, but who didn’t show any abnormalities on their ECG. We introduced a risk score, based on the ECG and a blood test to detect damage to the heart muscle.

As a result, we found that 30% of the people calling 112 with chest pain, don’t need emergency transport and can stay at home safely. That’s a tremendous saving and for the patient incredibly important as well,” Prof. Van ‘t Hof continues.

That’s the third big breakthrough, that after diagnostics and treatment, the care has now been expanded to different patient groups through triage.” Prof. Van ‘t Hof says.

What’s The Next Big Step?

The right care at the right location by transforming the ambulance into A&E.

With all these amazing achievements on myocardial infarction treatment, we wonder what the future will bring?

Prof. Van ‘t Hof shares his thoughts: “One study leads to another, that leads to another and so on. It’s becoming more interesting, even the Dutch health ministry wants to focus on the right care at the right location, using the ambulance for emergency care.    

Slowly but surely, the ambulance is turning into A&E (Accident and Emergency). They’re brilliant vehicles, harnessed with diagnostics equipment for ECG’s, ultrasounds and blood tests. To provide the exact same care that until recently was only possible at A&E.”

This will be the future: optimising the transformation of the emergency medical services into A&E.

Pre hospital phase clinical trials ambulance
Photo courtesy of Ambulance IJsselland

Dr. Arif Elvan, CEO Diagram Research, agrees: “We’re currently at the start of a transformation of the health care system. It focuses on transition of health care in general and on emergency care in particular. These changes are needed to keep the high quality care affordable and available to all patients in the Netherlands. The aim is to provide the best care to the patient at the right time and place.”

Prof. Van ‘t Hof foresees similar developments for ischemic stroke: “For myocardial infarction we use the expression ‘time is luck’, for cerebral infarction the common expression is ‘time is brain’. Every minute counts, but it has proven difficult to diagnose ‘ischemic stroke’ without a CT or MRI scan.

We’ve already seen mobile stroke units being developed: ambulances equipped with CT scans to diagnose and start treatment. And I’m definitely expecting further developments in this field.”

Ensuring Quality Care Throughout The Entire Care Chain

The beauty of ambulance studies is working together with people from the total care chain.

Looking at all the pre-hospital phase studies Prof. Van ‘t Hof has been involved in, we ask what he’s most proud of.

“The great collaboration,” he responds immediately. He explains: “The beauty of ambulance studies is working together with people from the total care chain. These studies prove the importance of quality care throughout the entire chain: care should already start with the emergency medical services and shouldn’t be limited to the hospital.

I’m extremely proud that through great teamwork, i.e. keeping each other posted of new developments and proactively seeking each other out, we are optimising this care chain.”  

Dr. Elvan underwrites the importance of teamwork: “We still need further improvement of medical treatment in the early phase of heart infarction. Close collaboration with ambulance staff is of paramount importance to develop novel on-site treatment strategies and improve outcome in these patients.”

Lastly, Prof. Van ‘t Hof adds that he’s also very proud of the studies they’ve performed, first On-Time 2 and now CELEBRATE. “The fact that CeleCor Therapeutics, the American company that initiated CELEBRATE, came to us. That’s wonderful.” he says.

Negotiating Health Insurance Challenges

We need financial coverage throughout the entire chain, without differentiation.

When asked, Prof. Van ‘t Hof shares his biggest challenge: the limited vision of the Dutch health insurance providers. He explains: “They only classify cases as in- or out-patient, two separate groups, where they only cover in-patient care. But they should look at the whole care chain.

Let’s take this pre-hospital triage study as an example: when the ambulance personnel determines a patient doesn’t need emergency transport and can stay at home safely, the patient is classified as out-patient thus not covered for medical expenses.

That doesn’t make any sense. It’s a dated financial structure that doesn’t fit today’s modern medical capabilities. It holds back progress. We need financial coverage throughout the entire chain, without differentiation. Unfortunately, pigeonholing is very common in health care.”

Is there hope, we wonder? “Fortunately, yes,” Prof. Van ‘t Hof answers. He talks about projects initiated by insurance providers, so-called ‘proeftuinen’ (sample gardens). When successful, the existing financial structure will be adjusted. And there are organisations that subsidise specific health care for which there isn’t a proper financial structure available yet.

2022 Pre-Hospital Emergency Care Conference

There isn’t enough attention for the entire care chain, for the interaction between ambulance and hospital.

Ultimately, we ask Prof. Van ‘t Hof what he hopes to achieve in the next few years, any new projects on the horizon?

Prof. Van ‘t Hof shares his ambition for 2022: “There isn’t enough attention for the entire care chain, for the interaction between ambulance and hospital.

It would be wonderful to organise a yearly global conference where we spark that interaction, join forces to see how we can push medicine forward together. A conference where we keep each other posted, inviting stakeholders for discussions, pulling in all the different parties that benefit from having the right care at the right location. Industries that manufacture equipment and blood tests and industries who need point of care equipment.

I strongly believe it would be a winning formula to join these different groups: the know-how, the expertise and the material men. And I’d love to be the front-runner in making it happen.”

Like to know more about pre-hospital phase studies?

It’s our mission to improve care for patient with an acute heart infarction. Trials in this field are one of the important pillars of our research institution.

Diagram has become an expert in coordinating and executing pre-hospital phase studies, working together with with an excellent network of renowned cardiologists, sponsors and everybody along the care chain from emergency medical services to the hospital.

Contact us here to discuss your project.

– Improving outcomes in heart patients, one heart at a time –

Pre hospital phase clinical trials Rutger van der Pijl 2
Photo courtesy of Rutger van der Pijl | Registered Ambulance Nurse, Ambulance IJsselland