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. 2021 Nov 8;27(3):848–856. doi: 10.1016/j.drudis.2021.11.002

Table 2.

Clinical trials investigating the effects of drugs targeting the PI3K/Akt/mTOR pathway in COVID-19.

Trial Status Last update Estimated enrolment Study start date Intervention/treatment Placebo comparator
NCT04371640: Safety and tolerability of Sirolimus adjuvant therapy in patients with COVID-19 Withdrawn (study population not regularly admitted to hospital; approaches have shifted away from repurposing old drugs) December 7, 2020 0 May 1, 2020 Sirolimus + standard medical care Day 1: 10 mg; Days 2–7: 5 mg Placebo + standard medical care Day 1: 10 ml Days 2–7: 5 ml
NCT04341675: Effect of sirolimus in improving clinical outcomes in hospitalized patients with COVID-19 Recruiting May 20, 2020 30 participants April 24, 2020 Sirolimus 6 mg daily on Day 1 followed by 2 mg daily for next 13 days for total treatment duration of 14 days or hospital discharge, whatever happens sooner Matching placebo + standard medical care
NCT04461340: The efficacy and safety of sirolimus as an adjuvant agent to the standard treatment protocol in patients with COVID-19 infection Recruiting September 9, 2020 40 participants August 15, 2020 20 patients will receive sirolimus (oral dose of 6 mg on Day 1 followed by 2 mg daily for 9 days) plus national standard-of-care therapy against COVID-19; daily administration of sirolimus (1 mg) for up to 4 weeks while hospitalized Matching placebo + standard medical care
NCT04482712: The clinical effectiveness of mTOR inhibition with rapamycin in minimizing or decreasing the ALI/ARDS in participants infected with mild to moderate COVID-19 infection Withdrawn (study was never submitted to IRB or approved because of feasibility issues) June 1, 2021 20 participants April 2021 Administration of rapamycin (sirolimus) 1 mg daily during hospitalization Matching placebo + standard medical care
NCT04374903: The clinical improvement in COVID-19 Patients treated with Hydroxychloroquine in Combination with Azithromycin or Sirolimus.: Not yet recruiting May 5, 2020 58 participants May 1, 2020 Subjects will receive either HCQ with azithromycin (AZ) or HCQ with sirolimus (SIR). Study A: subjects will receive HCQ 600 mg orally for 10 days and AZ 250 mg orally daily for 10 days; study B: subjects will receive HCQ 600 mg orally for 10 days and SIR 4 mg orally on Day 1, then 2 mg orally daily for 9 days Matching placebo + standard medical care
NCT04409327: Phase 2 Study to Determine if RTB101 Reduces the Severity of COVID-19 in Older Adults (≥65 years) Residing in Nursing Homes Terminated (insufficient accrual rate) February 10, 2021 36 participants July 11, 2020 Oral RTB101 (TORC1 inhibitor) 10 mg hard gelatin capsule once daily for 4 weeks Oral-matching placebo once daily for 4 weeks
NCT04584710: A Phase 2 Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Older Adults (≥65 years) Active, not recruiting February 9, 2021 60 participants October 13, 2020 Oral RTB101 (TORC1 inhibitor) 10 mg hard gelatin capsule once daily for 2 weeks Oral matching placebo once daily for 2 weeks
NCT04372602: The efficacy of the PI3K inhibitor Duvelisib in improving the overall survival and advanced disease manifestations of SARS-CoV-2 infection Recruiting May 25, 2021 28 participants October 12, 2020 Duvelisib 25 mg twice daily for up to 10 days Placebo 25 mg twice daily for up to 10 days