TMPRSS2 inhibitors for COVID-19

21st treatment shown to reduce risk in April 2021, now with p = 0.00063 from 29 studies.

Lower risk for mortality, ventilation, and recovery. 

No treatment is 100% effective.
Protocols combine treatments.

c19early.org

Meta-analysis

59 patient TMPRSS2 inhibitor late treatment RCT with results not reported over 3 years after completion.

7 TMPRSS2 inhibitors RCTs have results missing long after expected1-7
The trials report a total of 1,116 patients, with 3 trials having actual enrollment of 142, and the remainder estimated.

Important missing comments or errors? Let us know.

Study covers TMPRSS2 inhibitors and nafamostat.

1. Seydi et al., Multicentre, Open Label, Randomised, Adaptative Clinical Trial of Efficacy and Safety of Treatment Regimens in Adult COVID-19 Patients in Senegal, NCT04390594, clinicaltrials.gov/study/NCT04390594clinicaltrials.gov.

2. Kim et al., A Double-blind, Multi-center, Multi-regional, Randomized Controlled, Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of CKD-314 in Hospitalized Adult Patients Diagnosed With COVID-19, NCT04871646, clinicaltrials.gov/study/NCT04871646clinicaltrials.gov.

3. Boutboul et al., A Multicenter Randomized Trial to Evaluate the Efficacy and Safety of Camostat Mesylate for the Treatment of SARS-CoV-2 Infection - COVID-19 in Ambulatory Adult Patients (CAMOVID), NCT04608266, clinicaltrials.gov/study/NCT04608266clinicaltrials.gov.

4. Granados-Montiel et al., New prophylaxis regimen for SARS-CoV-2 infection in health professionals with low doses of hydroxychloroquine and bromhexine: a randomised, double-blind placebo clinical trial (ELEVATE Trial), BMJ Open, doi:10.1136/bmjopen-2020-045190.bmj.com, doi.org.

5. Bae et al., Treatment Effect of Nafamostat Mesylate in Patients With COVID-19 Pneumonia: Open Labelled Randomized Controlled Clinical Trial, NCT04418128, clinicaltrials.gov/study/NCT04418128clinicaltrials.gov.

6. Kim (B) et al., Open-label, Multi-center, Randomized Controlled, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of CKD-314 in Hospitalized Adult Patients Diagnosed With COVID-19, NCT04628143, clinicaltrials.gov/study/NCT04628143clinicaltrials.gov.

7. Mežnar et al., Use of Bromhexine and Hydroxychloroquine for Treatment of COVID-19 Pneumonia, NCT04355026, clinicaltrials.gov/study/NCT04355026clinicaltrials.gov.

Seydi et al., 8 Feb 2023, Randomized Controlled Trial, Senegal, trial NCT04390594 (history) (SEN-CoV-Fadj).

Late treatment
is less effective

Most accessed treatments

Antiviral effects

Vitamins & Minerals

Host endosomal entry / trafficking

Dual-action mAbs

RdRp

Nasal & Oral Sprays / Rinses

Analgesics

Antiandrogens

Host targets and pathways

Inflammatory and immune modulation

Mpro (Gen 1)

Oxidative stress and cytoprotection

Lifestyles

TMPRSS2

Spike neutralization

Replication inhibition (target unresolved)

COVID-19 mAbs

Pleiotropic modulation

Attachment / entry inhibition

Mpro (Gen 2)

H1RAs

Nutrients and microbiome support

Host mAbs

IL-6 / IL-6R blockade

Physical and extracorporeal interventions

Natural products and extracts

Symptom management

Unconfirmed antiviral rationale

Lifestyle, behaviors, and exposure prevention

Other complication management

Mpro / 3CLpro

Host pyrimidine synthesis

Direct viral inactivation

Endothelial / vascular protection

Direct respiratory tract treatments

Other antibodies, proteins, peptides, cells, and RNA therapies

Secondary infection and coinfection management

Multicentre, Open Label, Randomised, Adaptative Clinical Trial of Efficacy and Safety of Treatment Regimens in Adult COVID-19 Patients in Senegal

TMPRSS2 inhibitors for COVID-19