RECOVERY result:

Low dose steroids reduce mortality for COVID-19 patients requiring oxygen or ventilation.

But higher dose steroids increase risk of death in those with hypoxia but who do not require non-invasive or invasive mechanical ventilation.

medrxiv.org/content/10.110… Low-dose steroids (dexamethasone 6 mg daily) reduces mortality in patients with hypoxia (those receiving oxygen +/- ventilatory support)

nejm.org/doi/10.1056/NE…

Hot of the Press. Results from our latest trial.

Empagliflozin (originally a diabetes treatment) reduces risk of kidney disease progression (incl. dialysis) or cardiovascular death in pts with or without diabetes & regardless of level of kidney function

nejm.org/doi/full/10.10… 6609 pts with CKD (not requiring RRT)
Randomized to empagliflozin vs. placebo
- Half without diabetes
- One-third with eGFR <30 ml/min/1.73m2
- One-half with urinary albumin:creatinine ratio <300
- 2 years’ follow-up

1/3 reduction in risk of renal progression or CV death

RECOVERY Publication: ASPIRIN
(a widely used anti-platelet treatment in other settings)

14 892 patients hospitalised with COVID-19.

No impact on mortality.
Small improvement in hospital stay.
No impact on need for mechanical ventilation
6 more bleeds. 6 fewer thromboses (clots) Some will ask, why the study was so big.

The answer:
- Aspirin is cheap & widely available
- COVID-19 is common & mortality remains high
- Even a small reduction in the risk of death would have been incredibly important
- To detect small effects requires big randomised trials

*Making trials part of good clinical care*

Many have asked about secrets to the success of the RECOVERY trial.

What were the magic ingredients?
What are the lessons for the future?

This paper describes our approach - and sets out the actions needed:

ncbi.nlm.nih.gov/pmc/articles/P… Our approach - Quality by Design:

New Guidance for Smarter Randomized Controlled Trials

Open for consultation - please tell us what you think.

Highlighted in this article @DrugInfoAssn

globalforum.diaglobal.org/issue/septembe… As we highlight:

RECOVERY publication: Convalescent plasma in 11569 hospitalised patients
- no significant reduction in mortality
- no significant increase in chances of being discharged alive at 28 days
- no significant reduction in progression to invasive mechanical ventilation or death In post-hoc exploratory analyses.

No significant trend towards better outcomes by duration of symptom onset, level of respiratory support, or antibody status.

RECOVERY Pre-print:

Convalescent plasma does not improve survival in patients hospitalised with COVID-19 in this randomised controlled trial involving 11,558 patients:

medrxiv.org/content/10.110… No improvement in survival with convalescent plasma, regardless of patient antibody status at baseline:

RECOVERY Result for Tocilizumab
For patients with COVID-19, hypoxia & inflammation:
- reduces mortality
- shortens time to hospital discharge
- reduces the need for invasive mechanical ventilation

Good news for patients. Good news for the health services that look after them Benefits seen in wide range of patients (simple oxygen... mechanical ventilation)

Colchicine for non-hospitalised pts with COVID-19

Stopped by investigators “due to logistical issues related to maintaining the central study call center...
& ...perceived need to disseminate the study results rapidly”

Travesty.

medrxiv.org/content/10.110… The results are consistent with the size of benefit they set out to test.

But because they chose to stop early, the results are not significant and confidence intervals are wide.

So we're left with uncertainty.

RECOVERY Update:

30,000 patients now enrolled in one country in 10 months.

The most extraordinary effort.

And still ongoing. In the words of the independent Data Monitoring Committee:

"Thank you for your continuing help and support."

"RECOVERY is a beacon of light in these difficult times."

Latest results from RECOVERY trial: Azithromycin does not benefit patients hospitalised with COVID-19

No improvement in 28-day mortality, duration of hospital stay, or progression to invasive mechanical ventilation/ death.

recoverytrial.net/news/recovery-…

7764 pts randomised: This is an important result:
Azithromycin is on the WHO Watch Group of Antibiotics: antibiotics.

Widespread use of azithromycin for COVID-19 for which it is ineffective risks the development of resistance by bacterial infections for which it is effective.

WHO SOLIDARITY in full.

No significant improvement in survival with hydroxychloroquine, lopinavir, interferon, or remdesevir in hospitalised patients.

Negative results are important - allow us all to refocus drug development and health resources.

nejm.org/doi/full/10.10…

Results of the @WHO SOLIDARITY trial:

4 drugs tested in 11,266 patients with COVID in 405 hospitals in 30 countries:
- hydroxychloroquine
- lopinavir
- remdesevir
- interferon

No clear benefit of any of them on survival.

medrxiv.org/content/10.110… Similar results in different age-groups and whether on mechanical ventilation or not:

The @WHO SOLIDARITY trial is a major international achievement.

Knowing which treatments do not have meaningful impact on mortality is important - saves resources, refocuses scientific attention, benefits patients.

https://twitter.com/FinancialTimes/status/1316822064427339776

Doubtless there will be much discussion, not all of which will be as objective as we need in a pandemic.

But this trial is randomised, large, and focused on the ultimate clinical outcome - mortality.

More results from the RECOVERY trial - Hydroxychloroquine:

Among patients hospitalised with COVID-19, hydroxychloroquine (HCQ) did not improve 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death

nejm.org/doi/full/10.10… 1561 patients were randomised to HCQ + usual care
3155 patients were randomised to usual care alone
in the largest randomised trial of HCQ for treatment of COVID

Great summary of treatments for hospitalised patients with COVID-19 @rupert_pearse

threadreaderapp.com/thread/1312699… My take on this:

Dexamethasone improves survival.
Remdesivir shortens time to recovery.
Hydroxychloroquine & lopinavir are ineffective.

** we know because the clinical trials have been done**

Latest paper from RECOVERY trial:

In patients admitted to hospital with COVID-19, lopinavir–ritonavir did not reduce 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.

thelancet.com/journals/lance… Lopinavir-ritonavir is an HIV treatment that was widely recommended and used for #COVID19. The RECOVERY trial has shown it does not work - so doctors no longer use it.

That’s why we do trials - to separate out drugs we think might work from drugs we know do work.