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On 22 May 2020 the UK's MHRA (Medicines and Healthcare Products Regulatory Agency) asked us to pause recruitment to our COPCOV trial. We responded promptly to the MHRA, addressing their concerns in detail and await their decision, and remain confident that the trial will resume recruiting. The safety of our participants is our first priority, as is preventing illness in front-line NHS workers.

© Credit Supa-at Asarath

More information about COPCOV being currently paused

COPCOV key messages

Background

COVID-19 has caused hundreds of thousands of deaths during its first wave. Most experts anticipate ‘second waves’ in many affected regions - the disease is likely to stay with us for a considerable period of time.

Front-line healthcare workers and other hospital staff providing care for patients with COVID-19 are at increased risk of infection. It is crucial that they are protected against the disease. Adequate personal protection is key, but additional interventions could further lower the risk of infection. There are currently no vaccines nor drugs for the prevention of COVID-19. The World Health Organization recommends that outside the setting of a clinical trial we should not give healthcare workers any drugs claiming to prevent COVID-19 before we know that they are safe and effective.

The COPCOV study

COPCOV is a randomised, placebo-controlled prophylaxis study to determine whether chloroquine or hydroxychloroquine prevents coronavirus disease (COVID-19) in the healthcare setting.

The COPCOV study compares the drugs chloroquine and hydroxychloroquine against a placebo pill (not containing any drugs) for the prevention of COVID-19. Healthcare workers in participating centres who wish to join the study must provide consent and cannot have had COVID-19 before enrolment.

Half of the participants receive the drug, the other half receive placebo. The selection will be random. To enable unbiased assessments, neither the local study team nor the participant will know if they receive the drug or placebo tablets (“double blind”). All participants will also take the usual precautions for protection against the virus. Participants will take the study drugs each day for a period of three months, and will be followed closely to see how well the drug is tolerated, whether they contract the virus, and if they do, whether they develop mild or more severe COVID-19. If a participant develops COVID-19, they will be treated according to the treatment guidelines in their healthcare facility. The study aims to enrol 40,000 participants globally. We expect to have preliminary results available as to whether chloroquine or hydroxychloroquine can prevent COVID-19 by the end of 2020.

Chloroquine and hydroxychloroquine

The drugs used in this study, chloroquine and hydroxychloroquine, have shown in the laboratory to kill the novel coronavirus (SARS-CoV-2), the virus that causes COVID-19. The drugs have been in the news a lot because they have been tested in small trials for the treatment of COVID-19. Some of these studies claimed success, others failure, but all these studies were too small to give a definite answer about their efficacy or safety. Larger trials are ongoing to determine whether these drugs are effective for the treatment of COVID-19.

COPCOV is a very large study, enrolling 40,000 participants, and will give a definite answer whether the drugs are effective and safe. COPCOV studies chloroquine and hydroxychloroquine for the prevention of COVID-19, which is different from the treatment of patients that already have the disease COVID-19, who carry a much higher load of the virus.

Safety of the study drugs

Chloroquine and hydroxychloroquine have been used for the treatment of malaria for more than 60 years. Until recently approximately 300 million chloroquine malaria treatments were given annually. In total over 15 billion treatments have been taken. Chloroquine was also the antimalarial prophylaxis of choice for travellers to the tropics. They are also used at higher doses for the treatment of  other diseases such as rheumatoid arthritis and lupus.

These well-established drugs have an excellent safety record and are generally well tolerated. Side effects are usually mild and include stomach upset and nausea, headache and temporary blurring of vision. Chloroquine, more than hydroxychloroquine, can sometimes cause  itching.  If too high a dose is taken, these drugs can be dangerous or even cause death. They may cause toxicity to the eyes and muscles if taken regularly for years, but this does not occur with short term use (such as three months for prevention against COVID-19).

Chloroquine and hydroxychloroquine and cardiotoxicity (side effects on the heart)

In recent years there has been increasing concern about drugs which prolong the electrocardiograph QT interval. This is because some drugs which have this property predispose to a potentially lethal ventricular tachycardia called “torsade de pointes”. This is rare, but it has led to several drugs being withdrawn from the market. Chloroquine and hydroxychloroquine (and several other similar drugs) do prolong the QT interval but there is no convincing evidence that this has caused “torsade de pointes” in people with normal hearts. In fact, overall these drugs are anti-arrhythmic, and they have been used to treat people with atrial fibrillation. In the chronic treatment of lupus (which may affect the heart) patients receiving hydroxychloroquine have less arrhythmias than those receiving other drugs. Other drugs may also prolong the QT interval and combining these with chloroquine or hydroxychloroquine may be unwise, but for healthy people who are not taking regular medications which prolong the QT interval, there should be no concerns about cardiotoxicity.

Risk of getting COVID

COPCOV participants are not at a greater risk of developing COVID-19 when compared to other healthcare workers in similar settings.

Parallel developments expected during COPCOV

During the COPCOV study, evidence may emerge about the efficacy of various drugs for the treatment of COVID-19. This information will be very important, but is unlikely to answer the question of the COPCOV study: COPCOV is the only large-scale prevention study currently running and aims to determine if chloroquine and hydroxychloroquine can safely prevent COVID-19.

Also, there is an accelerated global effort to develop an effective vaccine to prevent COVID-19. Predicted timelines differ between experts, but a safe and effective vaccine in unlikely to appear before 2021. Sufficient production and distribution of a COVID-19 vaccine will be another important hurdle to reach the aim of global equitable access, particularly in rural hard-to-reach populations of resource-limited countries. We need all the tools at our disposal to protect our health workers and maintain resilient health systems. Potential drugs to prevent COVID-19, like the ones tested in COPCOV, will thus remain much needed.