A New Clinical Trial Asks: Can a Cholesterol Drug Help Slow Prostate Cancer?

Table of Contents

• Key Points
• Why This Research Matters
• Understanding Prostate Cancer and Hormone Therapy
• The Problem: Castration Resistance
• The Evidence Linking Cholesterol and Statins to Prostate Cancer
• What This Trial Aims to Prove
• Study Design and Methods
• Who Can Participate
• Measurements and Follow-Up Schedule
• Study Endpoints: What the Researchers Are Measuring
• Stored Blood Samples and Genetic Testing
• Sample Size: Why 400 Men?
• Ethics and Data Sharing
• Study Limitations
• What This Means for Patients Now
• Frequently Asked Questions
• Source Information

Key Points

• This phase III trial randomly assigns 400 men to 80 mg atorvastatin daily or placebo to see if it delays castration resistance during hormone therapy.
• Castration resistance is when prostate cancer progresses despite very low testosterone; it typically occurs within 12–15 months in men starting ADT for metastatic disease.
• Observational studies link statin use to about 30% lower prostate-cancer death risk and an 8–10 month longer response to hormone therapy, but randomized proof is lacking.
• The trial enrolls men starting long-term ADT for metastatic or high-risk recurrent prostate cancer who have not used statins recently; exclusion criteria include kidney or liver problems.
• No results are available yet; recruitment began in July 2019 and follow-up continues until progression, death, or 10 years, so conclusions await future publication.

Why This Research Matters

Prostate cancer (PCa) is the most commonly diagnosed cancer among Finnish men. It creates a major public health burden, causing roughly 900 cancer deaths every year in Finland alone. The yearly costs of the disease are estimated at 180 million euros.

Not all prostate cancers are life-threatening, however. Only about 10%–20% of prostate tumours eventually spread to other parts of the body (a process called metastasis) and reach a fatal stage. For men whose cancer does advance, the standard treatment is androgen deprivation therapy (ADT) — hormone therapy that lowers the body's male hormones, which prostate cancer cells need to grow.

The question this trial explores is simple but potentially powerful: if cholesterol helps prostate cancer grow and resist treatment, could a cholesterol-lowering drug called atorvastatin make the standard hormone therapy last longer?

Understanding Prostate Cancer and Hormone Therapy

Prostate cancer cells are sensitive to androgens (male hormones such as testosterone). This is the reason hormone therapy works against the disease. Androgen deprivation therapy (ADT, hormone therapy that reduces androgen levels) blocks or removes these hormones, starving the cancer cells and slowing their growth.

ADT is used in two common situations. Men who are diagnosed with metastatic prostate cancer (cancer that has already spread beyond the prostate) typically start ADT as their primary treatment. Men who had localised treatment (such as surgery or radiation) but later experience a biochemical recurrence — a rising prostate-specific antigen (PSA, a protein produced by the prostate that serves as a marker of cancer activity) — may also begin ADT as secondary treatment. PSA is a key monitoring tool: high levels suggest the cancer is active and growing.

There is a catch. As effective as ADT initially is, most advanced prostate cancers eventually find a way around it. The cancer adapts, changes, and resumes growing even when testosterone levels are extremely low. This is called castration resistance.

The Problem: Castration Resistance

Castration resistance is a landmark moment in prostate cancer care. It is clinically defined as the point when prostate cancer no longer responds to ADT treatment. Once that happens, doctors must switch to other, often more aggressive therapies.

The timeline for castration resistance is well documented but sobering. For patients who start ADT for metastatic prostate cancer, the median time to castration resistance is 12–15 months. The median time to death is 45 months in that group. For men who begin ADT because their cancer has recurred after primary treatment, the figures are better but still serious: a median failure-free survival time of 33 months and a median of 70 months until death.

Delaying castration resistance by even a few months could meaningfully extend both the period of good disease control and overall survival. This is precisely what the new trial attempts to do.

The Evidence Linking Cholesterol and Statins to Prostate Cancer

The idea that cholesterol matters for prostate cancer is backed by a growing body of research.

Laboratory evidence: Basic science studies have demonstrated that cholesterol is important for prostate cancer cell growth. Cancer cells ramp up their internal lipid (fat) production, and this increased lipid accumulation helps them survive in low-oxygen (hypoxic) conditions within the tumour — as mentioned in the original protocol. These lipid changes also help cancer cells evade the host's immune response. Crucially, laboratory work suggests that increased internal cholesterol production is central to the development of castration resistance itself.

Cholesterol as a risk factor: Blood cholesterol is likely a risk factor for prostate cancer prognosis. Men with hypercholesterolaemia (high blood cholesterol) face a significantly elevated risk of disease recurrence after primary treatment. Lipid metabolism — the way the body produces and uses cholesterol and other fats — is emerging as a new player in prostate cancer progression.

One of the key mechanisms is that cholesterol serves as the raw material (precursor) for the production of androgens inside the cancer cells themselves. Intracellular androgen production is a central route prostate cancer cells use to overcome ADT. The cholesterol-synthesising mevalonate pathway is also highly active in prostate cancer cells, and it produces not just cholesterol but also isoprenoid proteins that regulate cell growth. Statins block this pathway.

Observational evidence in patients: Use of cholesterol-lowering statin drugs has been linked to a lower risk of prostate cancer recurrence and progression. Statin users have a 30% lower risk of dying from prostate cancer compared with non-users. These findings come from observational studies, not randomised trials.

Statin use has also been reported to extend the effectiveness of ADT by approximately 8–10 months. In addition, observational data suggest statins are linked to a prolonged response to abiraterone and enzalutamide, two newer androgen-signalling-targeted drugs used once castration resistance has already developed.

Randomised evidence so far: Statins have not been shown to affect prostate cancer mortality in the large cardiovascular prevention trials that tested them. However, in those trials cancer patients were often excluded entirely. One randomised clinical trial that did focus specifically on prostate cancer patients found that 80 mg of atorvastatin daily, taken for a minimum of 21 days, reduced tumour proliferation activity compared with placebo. Similar results were seen after treatment with fluvastatin, though that study was not randomised or controlled.

Despite all this supportive evidence, no randomised placebo-controlled trial has yet tested whether statins can genuinely delay castration resistance in men on ADT. A recent post-hoc analysis (a re-analysis of a trial originally designed for another purpose) of a randomised clinical trial suggested that statin use was associated with lower overall and prostate-cancer-specific mortality in men receiving ADT. But the authors of this protocol insist that a purpose-built trial is the only way to answer the question properly, which is exactly what this study does.

What This Trial Aims to Prove

The primary objective of this phase III randomised double-blind placebo-controlled trial is to determine whether atorvastatin, compared with placebo, delays prostate cancer progression — specifically the development of castration resistance — in men receiving ADT for metastatic or recurrent prostate cancer.

The secondary objectives are broad:

• To test whether atorvastatin lowers prostate-cancer-specific or overall mortality compared with placebo
• To determine whether changes in blood lipid (cholesterol) levels during ADT predict disease recurrence
• To see whether serum lipid parameters reveal the occurrence of adverse tumour genetic traits that predict castration resistance

Study Design and Methods

The trial is a multicentre, randomised, double-blind, placebo-controlled phase III study. "Double-blind" means that neither the patient, nor the study nurses, nor the researchers know whether the patient is receiving the active drug or the placebo until the study is over. This design prevents bias.

The study will enroll a total of 400 men across collaborating urology departments:

• University hospitals and central hospitals in Finland
• Herlev University Hospital in Denmark
• Tartu University Hospital in Estonia
• Vestfold Hospital Trust in Norway

Eligible men are those who are about to start long-term ADT as either the first treatment for de novo metastatic prostate cancer (cancer present at the time of diagnosis that has already spread) or as treatment for a recurrence after localised therapy (e.g., surgery or radiotherapy). Participants may have high-risk M0 disease (cancer that has not yet spread to distant sites but carries high risk features) or M1 stage (cancer that has spread). The main requirement is simply that long-term ADT is being started.

Men are randomised in a 1:1 ratio — 200 receive atorvastatin and 200 receive placebo. Those in the active arm take 80 mg of atorvastatin daily, an established high-intensity dose. The placebo capsules are identical in appearance to the atorvastatin capsules.

Randomisation is performed without blocking or other restrictions. Only the national study coordinator in each country can see which study arm a participant has been assigned to. Everyone else — all researchers, study nurses and patients — remains blinded until the trial database is closed.

Treatment continues until one of three things happens: the patient develops castration resistance, dies, or reaches 10 years of treatment. The follow-up visits are scheduled at 6-month intervals, matching common clinical practice.

Importantly, participants who develop castration resistance are given the opportunity to continue their assigned study treatment (atorvastatin or placebo) in an unblinded fashion after the primary endpoint, to observe effects on long-term survival. This is based on prior evidence linking statins to longer cancer-specific survival.

Some practical details are worth noting. If a man begins a statin during the study for clinical reasons (for instance, his own doctor prescribes one for heart disease prevention), the study drug is stopped for that participant — but follow-up continues, and the participant is still included in the final analysis according to the intention-to-treat principle. This means the patient is analysed in the group to which he was originally randomised, regardless of whether he actually kept taking the study drug, preserving the scientific integrity of the randomisation.

If a participant experiences intolerable side effects, as judged by him or his physician, the study drug is stopped; those men are also analysed per the intention-to-treat principle. Participants who discontinue follow-up or deviate from the protocol for any reason are offered the chance to remain or to return to follow-up, again to support intention-to-treat analyses.

Unblinding — the moment when the treatment assignments are revealed — happens only after the recruitment target has been reached and every participant has been followed for a minimum of 12 months.

All clinical decisions apart from the study drug itself (e.g., whether to add early chemotherapy, abiraterone, or other drugs to ADT) remain with the attending clinician. These decisions are allowed and simply recorded in the electronic trial database.

Who Can Participate

The inclusion criteria are specific. Men must have:

• Histopathologically confirmed metastatic adenocarcinoma of the prostate, or high-risk M0 stage recurrent prostate cancer
• ADT or antiandrogen therapy initiated no longer than 3 months before recruitment (by the time they enroll, they may already be on treatment for a short period)
• Willingness to participate and signed informed consent

The exclusion criteria reflect safety and scientific purity. Men cannot participate if they:

• Use statins regularly at the time of recruitment or within 6 months before it (otherwise the trial couldn't measure the drug's effect cleanly)
• Have previously experienced adverse effects during statin therapy
• Have familial hypercholesterolaemia (a genetic condition causing very high cholesterol) or a very high total cholesterol level of 9.3 mmol/L or above
• Have clinically significant renal insufficiency (serum creatinine above 170 µmol/L)
• Have clinically significant liver insufficiency (serum alanine aminotransferase, or ALT, more than two times the upper limit of normal — ALT is a liver enzyme that rises when the liver is damaged)
• Take medications that can interact dangerously with statins, including St. John's Wort, HIV protease inhibitors, ciclosporin (an immune-suppressing drug), macrolide antibiotics, fusidic acid (an antibiotic), phenytoin, carbamazepine (anti-seizure drugs), dronedarone (a heart rhythm drug), or oral antifungal medication

One limitation noted by the study authors from the start: because only a minority of prostate cancer cases are advanced, and because a large share of potential participants are already on statins for cardiovascular reasons, enrolment will take several years — the study began in July 2019 and was still recruiting at the time of publication.

Measurements and Follow-Up Schedule

At each 6-month visit, the following are measured, as detailed in the protocol's schedule:

• Serum PSA (ng/mL) — the key cancer activity marker
• Lipid levels (mmol/L), including total cholesterol, high-density lipoprotein (HDL, "good cholesterol"), low-density lipoprotein (LDL, "bad cholesterol"), and triglycerides (another type of blood fat)
• Alkaline phosphatase (U/L) — an enzyme that rises when cancer has spread to bone
• Creatinine (µmol/L) — a measure of kidney function
• Fasting blood glucose (mmol/L) — to track how the drug and ADT affect blood sugar
• Serum creatine kinase (U/L) — a muscle enzyme monitored because statins rarely cause muscle damage
• Alanine aminotransferase (U/L) — a liver enzyme checked because statins rarely affect the liver

Compliance is actively monitored. At each visit, patients return the remaining capsules from the previous 6-month supply, and nurses count them. The count is recorded in the trial database.

The participant is also asked about symptoms suggestive of metastasis and about any adverse effects they may be experiencing.

Quality of life is assessed once a year using a validated questionnaire called the WHOQOL-BREF, a standard tool developed by the World Health Organization to measure well-being across physical, psychological, social and environmental domains.

Follow-up continues until castration resistance, dropout, death, or a maximum of 10 years.

The definition of castration resistance used in this trial is strict and follows international standards. It is defined as any of the following while serum testosterone is at castrate level (below 50 ng/mL or 1.7 nmol/L):

1. PSA progression: three consecutive rises of PSA measured at least 1 week apart, with two of the readings showing a greater than 50% increase over the nadir (the lowest PSA point), and the final PSA level above 2 ng/mL
2. Radiological progression: the appearance of two or more new lesions on a bone scan, or soft tissue enlargement as defined by standard RECIST criteria (a set of rules used to measure tumour response to treatment)

Study Endpoints: What the Researchers Are Measuring

The primary endpoint — the main outcome that determines whether the trial is a success — is the time to disease progression (development of castration resistance) after starting ADT or antiandrogen therapy.

The secondary endpoints are:

1. Prostate-cancer-specific mortality and overall survival
2. Change in serum cholesterol during the intervention and its role in predicting time to disease recurrence in the placebo arm
3. Occurrence of adverse tumour traits (predicting castration resistance) in circulating cell-free DNA — fragments of tumour DNA shed into the bloodstream
4. Changes in fasting blood glucose during ADT
5. Occurrence of cardiovascular events during ADT
6. Quality of life during ADT

Stored Blood Samples and Genetic Testing

The trial is not just a drug trial; it also has a translational science component. Separate whole blood samples (for RNA and DNA isolation), plasma, and serum are collected at every 6-month visit and stored for future analysis.

These samples will undergo:

• Lipidomics: mass-spectrometric and nuclear magnetic resonance (NMR)-based determination of the serum lipidome — the full profile of fats in the blood. This goes beyond standard cholesterol tests to examine many individual fat molecules at once.
• Genomic sequencing: RNA and whole-genome sequencing to look for mutations and genetic modifications that predict disease recurrence and metastasis. The protocol specifically names genes such as BRCA1/2, ERG, MYC, TP53, ATM, PTEN, and AR splice variants. AR stands for androgen receptor — the protein on prostate cells that androgens bind to, driving growth. Splice variants are abnormal versions of the receptor that can drive resistance even with low hormone levels.
• Hypoxia markers: measurements of low-oxygen conditions within the tumour, which drive aggressive behaviour.

For participants with confirmed bone or soft tissue metastases, the amount of cell-free DNA in the plasma is measured before ADT begins and again when castration resistance develops. Cell-free DNA is tumour DNA circulating freely in the blood; its levels can reflect tumour burden and genetic changes. In selected patients, researchers also perform positron emission tomography (PET, an imaging technique that uses radioactive tracers to visualise metabolic activity in tissues) scans with two special tracers: EF5, a radioactive compound that binds to hypoxic (oxygen-starved) tissue, to monitor hypoxia; and FDG-PET (fluorine-18-fluorodeoxyglucose PET) to evaluate immune responses in the primary tumour and metastases during atorvastatin treatment.

These analyses will clarify the role of lipid metabolism during ADT and may provide new tools for predicting and controlling disease progression.

Sample Size: Why 400 Men?

The number 400 was not chosen arbitrarily. It comes from a careful power calculation based on prior data.

In a cohort study by Harshman and colleagues, among men starting ADT, 58% of statin users progressed to castration resistance during a median follow-up of 5.8 years, compared with 75% of non-users. In plain terms, this means that about 58 out of every 100 statin users saw their cancer become resistant within that time period, versus 75 out of every 100 non-users.

Using those percentages, with standard statistical thresholds of alpha set at 0.05 (the accepted 5% risk of a false-positive result) and beta at 0.20, the trial is powered at 80% (meaning an 80% chance of detecting the effect if it truly exists). A sample size of 400 men is sufficient to detect a hazard ratio (HR) of 0.65 — that is, a 35% relative reduction in the risk of progression at any given time point for the atorvastatin group. The calculation also assumes a 10% dropout rate in each study arm.

An HR of 0.65 is a meaningful effect size. It means that, at any given moment during follow-up, a man on atorvastatin would have a 35% lower chance of having progressed to castration resistance than a man on placebo. Using the Harshman data as context: if 75% of placebo patients progress, roughly 49% of atorvastatin patients progressing would represent that magnitude of benefit. The software used for the calculation was "PS—Power and sample size," V.3.1.2.

To put the expected timelines in perspective: the median time to progression is assumed to be 12–15 months for patients with de novo metastatic disease, and 33 months for patients treated for recurrence after localised therapy. That means the trial will need many years of follow-up before final results are available.

Ethics and Data Sharing

The study was approved by the Regional Ethics Committees of the Pirkanmaa Hospital District (Science Centre, Tampere, Finland, approval number R18065M) and of Tartu University Hospital in Estonia (approval number 319/T-6).

Every participant reads and signs an informed consent form before entering the study. Informed consent in this context means the patient is given clear, plain-language information about the trial — its purpose, procedures, risks, and benefits — and voluntarily agrees to participate before any study-specific procedure begins.

Data are collected and managed using REDCap, a secure electronic data capture platform hosted at Tampere University. Access is restricted to the primary investigators, study nurses, and registered co-investigators at each site. The database records laboratory results, symptoms, imaging findings, and all clinical decisions including the use of chemotherapy or other drugs alongside ADT. The study monitors compliance by capsule counts and systematically records adverse effects and symptoms suggestive of metastases on every visit.

After the primary endpoint results are published, the investigators have committed to making anonymised summary metadata and the statistical code openly available. No information that could identify a participant will be included. The trial is registered in two public registries — Clinicaltrials.gov (NCT04026230) and the European Eudra-CT registry (2016-004774-17) — which is standard practice for clinical trials to promote transparency.

Men who develop intolerable side effects may stop the study drug but remain in the trial for follow-up. Similarly, patients whose clinical doctors initiate statin therapy during the trial are taken off the study drug but kept in the analysis. These design choices reflect the intention-to-treat principle, which keeps the randomisation intact and avoids bias in estimating the true effect of the intervention.

Study Limitations

The study authors openly acknowledge several limitations in their published protocol:

Slow recruitment: As a limiting factor, only a minority of prostate cancer cases are advanced enough to qualify. A large proportion of potential participants are ineligible because they already use statins. As a result, study enrolment will take several years. The trial began enrolling in July 2019 and was still recruiting when the protocol was published in April 2022.

Population generalisability: Because men already on statins are excluded, the trial population will consist of statin-naïve men. The results may not apply to men who are already taking statins when they start ADT.

Open-label decisions after progression: After the development of castration resistance, patients may continue their assigned treatment, but decisions about subsequent cancer therapy (e.g., chemotherapy or abiraterone) are made by clinicians on a case-by-case basis. This adds real-world variability that could influence the survival analyses.

Estimated effect size: The power calculation is based on observational data, and observational estimates can be inflated by confounding factors — differences between statin users and non-users that have nothing to do with the statin itself (for example, statin users may see doctors more often). The true effect may turn out to be smaller than the HR of 0.65 used in the calculation. If the real effect is weaker, a trial of 400 participants might not be statistically powerful enough to detect it. Conversely, if the effect is real, it will show clearly.

None of these limitations undermines the trial's purpose. They simply reflect the realities of running a rigorous study in this patient population.

What This Means for Patients Now

This trial is a study protocol, not a result. No outcomes are available yet, and no conclusions can be drawn about whether atorvastatin actually delays prostate cancer progression. What this protocol does offer is a clear and detailed roadmap for answering a question that has been building for years across laboratory, observational, and small clinical studies.

The biology is plausible, and there is a solid chain of evidence linking cholesterol metabolism to prostate cancer growth and treatment resistance. Prior observational studies suggest statin use is associated with approximately 30% lower prostate-cancer-specific mortality and with an 8–10 month prolongation of ADT effectiveness. But correlation is not causation, and observational data can mislead. The only way to establish that statins truly help is through a randomised controlled trial like this one — the gold standard of clinical evidence.

For patients with prostate cancer today, the practical takeaways are:

• The study drug is a high-intensity statin dose (80 mg atorvastatin daily), a dose that is already widely prescribed and has a well-established safety profile when monitored correctly.
• The trial explicitly monitors muscle enzymes (creatine kinase), liver enzymes (ALT), and blood glucose at every visit, reflecting standard statin safety monitoring. Patients on statins sometimes experience muscle aches; serious side effects such as rhabdomyolysis (severe muscle breakdown) or liver injury are rare.
• Patients currently on ADT who are interested in cholesterol management should discuss it with their oncologist or urologist. Guidelines for cardiovascular risk reduction apply to prostate cancer patients just as they do to anyone else.
• This trial is being conducted in Finland, Denmark, Estonia, and Norway. Eligible patients in those countries — men with metastatic or high-risk recurrent prostate cancer starting long-term ADT who are not already on statins — may wish to ask their urologist whether participation is possible at their centre. The study's public contact is Tampere University Hospital in Finland (Teemu Murtola, MD, PhD).
• Results will take several years. Recruitment began in July 2019, and the planned follow-up runs until progression, death, or 10 years. The unblinding will occur after the target of 400 participants is reached and all have been followed for a minimum of 12 months.

The broader message is reassuring. The scientific community is actively looking for safe, inexpensive, and widely available tools to make existing prostate cancer treatments last longer. A drug like atorvastatin, which is already taken by millions of people worldwide for heart health, would be a particularly attractive addition if proven effective — not a replacement for ADT, but a possible companion therapy.

Until the results are in, patients and doctors should continue to base treatment decisions on proven therapies and on established guidelines for managing cholesterol and cardiovascular risk. This trial is one to watch, for the answer it may provide and for the careful methodology it demonstrates.

Frequently Asked Questions

Who can join this clinical trial?

Men with metastatic prostate cancer or high-risk recurrent prostate cancer who are about to start long-term hormone therapy (ADT) are eligible. They must not have used statins within 6 months before joining. Other health conditions and medications may also affect eligibility, so patients should ask their urologist.

What is castration resistance and why does it matter?

Castration resistance means prostate cancer stops responding to hormone therapy and starts growing even when testosterone levels are very low. Once this happens, doctors need to switch to other treatments. Delaying this point could extend good disease control and possibly survival, which is what the trial aims to test.

What treatment do participants receive in this trial?

Participants are randomly assigned to take either 80 mg of atorvastatin daily or an identical-looking placebo pill. Neither the patient nor the researchers know which one they receive until the study is unblinded. Treatment continues until castration resistance develops, death, or a maximum of 10 years.

What are the main side effects or risks of atorvastatin?

Atorvastatin is a widely used cholesterol drug with known side effects. Some patients experience muscle aches; serious side effects like severe muscle breakdown (rhabdomyolysis) or liver injury are rare. The trial monitors muscle enzymes, liver enzymes, and blood glucose at every 6-month visit to check for problems.

How long will the trial last and when will results be known?

Recruitment began in July 2019 and was still ongoing in April 2022. Each participant is followed for at least 12 months after the last patient enrolls, with follow-up continuing until castration resistance, death, or 10 years. Final results will take several years to become available.

If a participant develops side effects, can they stop the study drug?

Yes. If a participant experiences intolerable side effects, as judged by him or his physician, the study drug is stopped. However, the participant remains in the trial and continues follow-up. Their data are still analyzed in their original treatment group according to the intention-to-treat principle.

What does the trial measure to decide if atorvastatin works?

The main measure is time to castration resistance, defined by PSA increases or new lesions on imaging. Secondary outcomes include prostate-cancer-specific death, overall survival, changes in cholesterol levels, blood sugar, quality of life, and cardiovascular events. Researchers also collect blood samples for genetic and lipid analyses.

Should I get a second opinion about taking atorvastatin to help keep my prostate cancer from becoming resistant to hormone therapy?

Seeking a second opinion is reasonable before adding any new drug to standard hormone therapy for advanced prostate cancer. No trial results yet show that atorvastatin delays castration resistance. Observational data associate statin use with a 30% lower risk of dying from prostate cancer and an 8–10 month extension of hormone therapy effectiveness, but those findings are not proof. This randomized trial directly tests atorvastatin 80 mg versus placebo. A second opinion can clarify whether you meet the trial's eligibility criteria and whether lipid management fits your overall treatment plan. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: clinical study testing impact of atorvastatin on prostate cancer progression

Authors: Aino Siltari, Jarno Riikonen, Juha Koskimäki, Tomi Pakarainen, Otto Ettala, Peter Boström, Heikki Seikkula, Andres Kotsar, Teuvo Tammela, Mika Helminen, Paavo V. Raittinen, Terho Lehtimäki, Mikkel Fode, Peter Østergren, Michael Borre, Antti Rannikko, Timo Marttila, Arto Salonen, Hanna Ronkainen, Sven Löffeler, and Teemu J. Murtola

Publication: BMJ Open, 2022, volume 12, issue 4, article e050264. Published online 29 April 2022. DOI: 10.1136/bmjopen-2021-050264

Trial registrations: Clinicaltrials.gov NCT04026230; Eudra-CT: 2016-004774-17; protocol code ESTO2

This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and does not constitute medical advice. Patients should consult their healthcare providers about any questions regarding their treatment.