I explained earlier the potential benefits of NO in treatment of covid19
I also suggested that Tadalafil oral tablets once daily is a good option for that purpose as Tadalafil leads to accumulation of NO in pulmonary circulation which improves lung perfusion, washing toxins and might has an antiviral effect on covid19 as was proved in SARS
I invite world health organization to lead clinical trial/s on tadalafil as a potential therapy for covid19
I also invite all local health authorities in all countries to start such clinical trials
There are many scientific evidences supports the potential benefits of tadalafil while there are hundreds of clinical trials testing many compounds even nicotine and cannabis!
I made a suggested protocol for a clinical trial testing tadalafil in treatment of covid19
It is available for everyone for free:
Investigating if tadalafil daily tablets will have a role in treatment of Covid19 infection
Introduction: Tadalafil, the first once-daily PDE5 inhibitor FDA approved (2009) for the treatment of pulmonary artery hypertension (PAH), has been shown to improve exercise tolerance, pulmonary hemodynamics, and quality of life. The drug is well tolerated and carries with it a favorable side effect profile. The production of cyclic guanosine monophosphate (cGMP) by activation of guanylate cyclase by NO in turn activates protein kinase G (PKG) that decreases pulmonary artery smooth muscle cell calcium and potassium levels leading to pulmonary artery vasodilation, decreased smooth muscle cell proliferation, and increased apoptosis of pulmonary artery smooth muscle cells.
As PDE5 leads to degradation of cGMP, a selective PDE5 inhibitor would have numerous downstream benefits including pulmonary artery vasodilation, decreased pulmonary vascular resistance and ultimately increased cardiac output. Additionally, PDE5 inhibitors may augment right ventricular function though their inhibition of phosphodiesterase 3.
Phosphodiesterase type 5 is located primarily in pulmonary artery smooth muscle cells and in the penile circulation. Its main role is to degrade cGMP located in these tissues. The relative paucity of PDE5 in the systemic vasculature makes this an attractive therapeutic target as one would expect minimal systemic vasodilation as opposed to nonselective vasodilators such as calcium channel blockers which cause prohibitive hypotension in most patients with PAH.
In adults with pulmonary hypertension, inhaled nitric oxide dilates the blood vessels of the lungs without affecting blood vessels elsewhere, making it a safe way to relieve high blood pressure.
In 2004, researchers at the University of Leuven in Belgium discovered yet another property of nitric oxide: It killed coronaviruses.More specifically, it killed the coronavirus that leapt from bats to humans and sparked the 2003 epidemic of severe acute respiratory syndrome(SARS).In African green monkey cells that had been infected with the SARS coronavirus, an organic nitric oxide compound cut the virus’s ability to replicate in half. A year later, Swedish scientists confirmed the finding and found that the higher the dose, the better the gas worked to shut the SARS virus down.
This substance(NO) has a wide range of biological properties that maintain vascular homeostasis, including modulation of vascular dilator tone, regulation of local cell growth, and protection of the vessel from injurious consequences of platelets and cells circulating in blood, playing in this way a crucial role in the normal endothelial function.This mechanism is another attractive property to NO in treating patients with Covid19 infection as one of the theories include vascular thrombosis
Now Sildenafil is being explored as a treatment for COVID-19. A pilot study in China is testing the drug in COVID-19 patients with breathing troubles who do not yet need mechanical breathing assistance.Like nitric oxide, sildenafil, dilates blood vessels. The Chinese scientists investigating it believe it may help open the tiny vessels that draw oxygen from the lungs, allowing patients to overcome the respiratory distress that occurs in some cases of COVID-19.
The longer half-life of tadalafil (17.5 hours) when compared with sildenafil (4 hours) may represent an attractive option to some patients as it may allow for less frequent dosing and a more sustained benefit.
Our hypothesis is that Tadalafil 20-40 mg once daily might have a positive effect in patients suffering from Covid19
2nd aim it might have a protective effect in healthcare practitioners who are at high risk of catching the infection if they take tadalafil 20 mg in addition to other precautions
Study design: A prospective randomized double blinded placebo-controlled study constitutes 3 groups,2 active arms and one placebo: group A patients receive 20 mg Tadalafil once daily; group B receive 40mg Tadalafil once daily and group C receive placebo one tablet once daily.
Sample size: to be calculated according to the location but we can start with 200 patients in each group.
Inclusion criteria: patients diagnosed with Covid19,both sexes ³18 years old
Exclusion criteria: patients who are taking nitrates and patients with hepatic dysfunction
Primary Outcome Measures :
- Reduction in the incidence of patients with mild/moderate COVID-19 requiring intubation and mechanical ventilation [ Time Frame: 28 days ]
The primary outcome will be the reduction in the incidence of patients requiring intubation and mechanical ventilation, as a marker of deterioration from a mild to a severe form of COVID-19. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.
Secondary Outcome Measures :
- Mortality [ Time Frame: 28 days ]
Proportion of deaths from all causes
- Time to clinical recovery [ Time Frame: 28 days ]
Time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air), alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent) and resolution of hypoxia (defined as SpO2 ≥ 93% in room air or P/F ≥ 300 mmHg). All these improvements must be sustained for 72 hours.
Other Outcome Measures:
- Negative conversion of COVID-19 RT-PCR from upper respiratory tract [ Time Frame: 7 days ]
Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or oropharyngeal swab.
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