Adaptive COVID-19 Treatment Trial (ACTT) [COVID-19] [UPH]
Research type
Research Study
Full title
A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalised Adults
IRAS ID
281800
Contact name
Sarah Pett
Contact email
Sponsor organisation
Regents of the University of Minnesota
Eudract number
2020-001052-18
ISRCTN Number
ISRCTN13035264
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 9 months, 7 days
Research summary
Research Summary
This multi-centre trial (ACTT/INSIGHT-10) is a double-blind placebo-controlled trial, of the antiviral drug, remdesivir, for the treatment of COVID-19 infection in adults in hospital. This means neither the patients nor doctors know who is receiving remdesivir and who is receiving a drug containing no active ingredient (placebo). In total, at least 800 patients from approximately 100 sites in the USA, Mexico, UK, Europe, and SE Asia will be included in the trial. All patients will receive normal hospital treatment as well as one of the following treatments, assigned by chance: 1) daily intravenous infusion of remdesivir (active drug) - there is a 1 in 2 chance of being in this group; and 2) daily saline infusion (placebo infusion with no active ingredient) -t here is a 1 in 2 chance of being in this group. Treatment will be given for a maximum of 10 days and only whilst the patient is in hospital. The trial will last for 29 days. The main way of seeing how well the treatment works will be the time to recovery over 29 days of follow-up. Getting better (recovery) in the trial was defined as being still in the hospital and off oxygen, or out of hospital and either back to partial or complete return to health status before getting COVID-19. \n Patients will have clinical, safety and laboratory measurements taken up to 7 times during the study, in patients who have left hospital the visits at Day 15, 22 and 29 can be done on the phone, rather than asking patients to come back in for review. Optional blood samples will be taken to assess safety and to measure virus levels, immune response (body’s defences) and inflammation levels. These samples will be taken on Day 1 of the trial (before treatment), on Days 3, 5, 8, 11 (whilst in hospital) and also on Days 15 and 29, if patients are still in hospital on these days. Swabs from the mouth and throat (oropharyngeal) will be taken on the same days to measure the virus levels later on. High-level results for the first stage of the trial were reported on 29th April 2020. These showed remdesivir sped up recovery from COVID-19. This resulted in a fast track emergency approval by the drug regulatory authorities in the USA (the FDA) of remdesivir for patients hospitalised with COVID-19, meeting the following criteria: proven or suspected COVID-19; in hospital; on mechanical ventilation or receiving Oxygen therapy or having low oxygen levels without Oxygen therapy.Summary of Results
What was the ACTT-EU/UK trial about?
ACTT-EU/UK was testing how best to treat COVID-19.Stage 1 compared a new drug called remdesivir to a placebo (dummy) treatment. It aimed to see if remdesivir could help people in hospital with COVID-19 recover faster. Remdesivir is a drug that was developed to treat other viruses. Remdesivir might help people who are seriously ill with COVID-19, but we needed to test it to find out if it works.
Stage 2 compared a drug called baricitinib (used for the treatment of rheumatoid arthritis) plus remdesivir to giving remdesivir alone in hospitalized patients with COVID-19.
Why was the ACTT-EU/UK trial needed?
COVID-19 is caused by a new virus that affects people’s breathing. While some people may have no symptoms, or only mild symptoms, other people may become seriously ill. Sadly, it has already caused deaths around the world.
As COVID-19 is caused by a new virus, we do not yet know how best to treat it.
Who took part in the ACTT-EU/UK trial?
People taking part in the ACTT-EU/UK trial were adults who had been admitted to hospital with COVID-19. The trial took place in hospitals in the USA, South East Asia, the UK, Greece, Denmark, Spain and Germany. Five hospitals in the UK took part.
How was the ACTT-EU/UK trial carried out?
The ACTT-EU/UK trial stage 1 recruited patients in March and April 2020. 1063 people took part in the study, including 46 from the UK. People who agreed to take part in the trial were randomised into 2 groups. People were allocated at random. Neither they nor their doctors knew which group they were in. Half were in the remdesivir group; half were in the placebo group. They either received remdesivir or the placebo, via a drip, for up to 10 days while they were in hospital.
We followed up on how people were doing for 29 days. We wanted to see if remdesivir sped up recovery from COVID-19 compared to the placebo. We looked at the side-effects people had. We also wanted to see whether remdesivir reduced:
• the need for ventilation or supplemental oxygen
• how long people needed to stay in hospital
• deathsThe ACTT-EU/UK trial stage 1 found that people who had remdesivir recovered quicker from COVID-19 than people who had the placebo. People in the remdesivir group took on average 11 days to recover. People in the placebo group took 15 days to recover, on average. This difference is big enough for us to be confident that remdesivir is better than placebo in improving time to recovery. There was also some evidence that remdesivir may reduce deaths. 8 out of every 100 people in the remdesivir group died, compared to almost 12 out of every 100 people in the placebo group. However, we do not yet have enough data to be sure this difference was due to remdesivir.
The ACTT-EU/UK trial stage 2 recruited more than 1000 patients in May 2020 with one participant from the UK. People who agreed to take part in the trial were randomised into 2 groups. One half were randomised to active baricitinib tablets, the other half placebo tablets. People were allocated at random. Neither they nor their doctors knew which group they were in. As the results in ACTT-1 had shown a benefit of remdesivir, everyone also received remdesivir via a drip, for up to 10 days while they were in hospital.
We followed up on how people were doing for 29 days. We wanted to see if baricitinib plus remdesivir sped up recovery from COVID-19 compared to remdesivir alone.
People who had baricitinib in combination with remdesivir compared to those treated with remdesivir alone had an approximately one-day reduction in their recovery time, indicating that the combination of baricitinib plus remdesivir was of clinical benefit.
These results could help improve how future patients with COVID-19 are treated.Publications
ACTT-1 final results (ACTT-1_final_resultspaper_
nejm_08Oct2020.pdf)
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbaOaXkqnUjlBKwgJSG2SREygX03twdhCJHwK3ZjVYWdGLQ2WY7CTCyiiooQKxoasEQ-3D-3DkAax_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIWDhTy2QSghyDiOoobn0XtlmAR-2BDtCAzTEX99uGr-2FwdmdX2S2-2FDNq6sVqJaz9h3J7iIgNdrDHb0SwU0oU-2BXg-2FZB8fbWac7GupmVx7hoO-2BzFTquKUnAWijA1Le5bkHSFZnacZprcBySZTWnQh5xnB3vTuFca1glRX9xP7ZwwcEYlA-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C8c294c68b68e47cf147608d9a822272c%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637725686900433587%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=EQ5WL8UYB59QEN7F84V5kPWjsFciGzRYMMM%2Fg2e8WJI%3D&reserved=0
ACTT-2 results
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbUn9xEtYMEd9K4yXnu-2Bh8zWKJDCqaBxzUDe8CybQHnk2TKqQWzU3oReOiXLvPE641yGVShiFmG8v6yRaoHQ00L058WzT9XDePla7mORVnsZt9lTsaZFO2TaMcSGnSEvV0YcToDIAickyYlSOIj8-2ByrY-3DFWvC_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIWDhTy2QSghyDiOoobn0XtapdILYyD-2FK-2F3s0LuYFbgbEhr8ONJe0x2zOaPFFhK8T0y13y1Ukf0-2Bu8T5J9xRe17BJUJ9rpxyRdIabb2Js1N-2FeEH2PHHpe7VfklxALzuoqlkAbx2RTpnytRH5K20opeCRu0PobTyGPHWcA1txCtEcA-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C8c294c68b68e47cf147608d9a822272c%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637725686900433587%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=ZZVxWsURZKK0blmG0FyvabCW7F2A4SPsoIa97CuXnP0%3D&reserved=0REC name
South Central - Hampshire B Research Ethics Committee
REC reference
20/SC/0154
Date of REC Opinion
26 Mar 2020
REC opinion
Favourable Opinion