Clinical trial NCT04465604: Hypertonic Saline for COVID-19 Symptoms
Official title: HYPERTONIC SALINE COATED FACE MASK FOR REDUCING RESPIRATORY SYMPTOM SEVERITY IN PATIENTS WITH COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: COVID-19
Lead sponsor: King Faisal Specialist Hospital & Research Center
Sponsor class: OTHER
First posted: 2020-07-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The sample size was based on the following assumptions: Poor response rate to HTS is set at 10% or less; Good response to HTS is set at 30% or more ;One-sided Alph error probability is set to \< 0.05 (i.e. p \< 0.05) and Power to detect rate difference between good response and poor response to HTS is at least 80%. Using the Fleming single-arm group-sequential design (Fleming 1982) Based on these assumptions; a sample size of N=25 patients is expected to achieve a power of 84% of detecting enough activity by HTS (p\<0.05 one-sided) of improving respiratory parameters of COVID19 patients. This will be achieved if the true remission rate difference between a poor and good HTS is 20%. Considering the dropout rate of 25%, a minimum of 50 patients will be enrolled. This will ensure more than 90% power to detect at least 20% positive effect of HTS
Primary purpose: TREATMENT

Brief summary: Rationale:

Coronavirus disease 2019 (COVID-19) is spreading rapidly in the world with no proven effective therapy to date. Some patients with COVID-19 develop sever respiratory disease requiring ICU care. There is in vitro evidence that hypertonic saline (HTS) may be beneficial in reducing the inflammatory component in similar viral illnesses.

Objective:

To assess whether wearing a face mask sprayed with HTS (in addition to other COVID-19 treatments) leads to decreasing the severity of the respiratory symptoms resulting from COVID-19.

Study design:

Multi-centre trial

Study population:

Any patient older than 18 years of age with confirmed COVID-19 diagnosis who has any of the following respiratory symptoms or signs:

* cough,
* shortness of breath,
* tachypnea (respiratory rate of 20 breaths / minute or more),
* hypoxemia (O2 saturation 90% or less on room air)

Intervention:

Participants will be asked to wear a face mask for 20-30 minutes every 6 hours for the duration of their respiratory symptoms and/or signs. This inside surface of the face mask will be sprayed with 10-15 ml of HTS and allowed to air dry before the participant is permitted to wear it. A new face mask will be given to the patient every 24 hours. All participants will continue to receive their other COVID-19 treatments as per local hospital guidelines.

Main study parameter:

Improvement of the respiratory symptoms and signs on repeated measurement.

Nature and extent of the burden and risks associated with participation, benefit:

The burden of COVID-19 is very severe world wide. The trial duration is 3 months, with potential extension if deemed needed by interim analysis at the end of 3 months. There are no additional risks for participation in this study as only face masks will be used with no additional medications being given to the participants. In the future, the results of this study could lead to improved care for COVID-19 patients.

Detailed description: Since its emergence as severe outbreak in China in December 2019, coronavirus disease 2019 (COVID-19) has spread so rapidly in the world that more than 780,000 cases have so far been reported worldwide and since then the WHO has declared it as a pandemic. The rapid spread of the disease is imposing major threats on healthcare systems in many countries in the world The major threat to these healthcare systems so far has been the large number of patients who will need respiratory support (ventilators) because of the severe lung injury associated with COVID-19.This disease shares similar pathogenetic, epidemiological and clinical features to the two previously reported coronavirus epidemics (severe acute respiratory syndrome \[SARS\] and Middle East respiratory syndrome \[MERS\]) to COVID-19. However little is currently known about SARS-CoV-2 with no established therapy or vaccine.

Lai et al in their 2005 publication showed that "Even with a relatively high virus load (SARS-CoV) in the droplet, rapid loss of infectivity was observed for paper and cotton material" and that "all disinfectants (used in the study) reduced the virus load (SARS-CoV) by 13 log within 5 min after incubation". In addition, it has been shown that viruses (including corona family of viruses) can be de-activated when they come in contact with surfaces covered with sodium chloride (table salt). This can be explained by "physical destruction of virus during recrystallization of coated salts. When the salt-coated fiber is exposed to virus aerosols, salt crystals below the aerosol droplet dissolve to increase osmotic pressure to virus. Due to evaporation, the salt concentration of the droplet significantly increases and reaches the solubility limit, leading to recrystallization of salt. As a consequence, virus particles are exposed to increasing osmotic pressure during the drying process and are physically damaged by crystallization." In 1961, Spier et al showed that viral replication is inhibited by the presence of chloride / halide salts. In addition, a recent report showed that non-myeloid cells (e.g. epithelial, fibroblast and hepatic cells) have an innate immune mechanism, which is augmented in the presence of salt (NaCl). The same report also showed that, in cell culture models, DNA, RNA, enveloped and non-enveloped viruses are all inhibited in the presence of NaCl. The antiviral effect was dependent on the availability of chloride ions (and not sodium ions). In the presence viral infection and the availability of NaCl, cells utilize the chloride ions to produce hypochlorous acid (HOCl). Since HOCl is the active ingredient in bleach, which is known to have an antiviral effect, the mechanism could be augmented by supplying chloride ions through NaCl to treat viral infections. The Edinburgh and Lothians Viral Intervention Study (ELVIS), a pilot RCT of hypertonic saline nasal irrigation and gargling (HSNIG) versus standard care in adults with URTI showed a reduction in the duration of illness by 1.9 days (p = 0.01), less over-the-counter medications use by 36% (p = 0.004), less disease transmission within household contacts by 35% (p = 0.006) and less viral shedding by ≥0.5 log10/day (p = 0.04).

Hypertonic saline (HTS) has also been shown to have anti-inflammatory effects on lung epithelium. In addition, inhaled HTS has been shown to have beneficial effects when used for patients with lung diseases (e.g. cystic fibrosis).

Therefore, the combination of the antiviral properties on surfaces and the anti-inflammatory effects of HTS renders such widely available, affordable and cheap therapy amenable for exploring as potentially beneficial in reducing the severity of lung injury in patients with symptomatic COVID-19 with very minimal risk to the patients.

This proposal aims at testing the effect of spraying the routinely used face masks (or for that matter any material to cover nose and mouth) with HTS on the severity of respiratory symptoms and signs of patients with confirmed COVID-19. In addition, the rate for ICU utilization will be monitored.

Eligibility criteria: Inclusion Criteria:

* Age 18 years and older
* confirmed diagnosis of COVID-19 by PCR and
* Any of the following

  * cough
  * shortness of breath
  * Respiratory rate more than 20 per minute or
  * oxygen saturation 90% or less on room air

Exclusion Criteria:

* Age younger than 18 years
* Pregnancy
* Participation in other COVID-19 intervention trial

Primary outcomes:
measure: Improvement of respiratory symptoms
timeFrame: Throughout hospital stay on average 21 days
measure: Improvement of respiratory signs
timeFrame: Throughout hospital stay on average 21 days
Secondary outcomes:
measure: ICU admission
timeFrame: Throughout hospital stay on average 21 days
measure: Mechanical ventilation
timeFrame: Throughout hospital stay on average 21 days
Other outcomes:
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital and Research Center
Study officials:
affiliation: King Faisal Specialsit Hospital and Research Center
name: Ali Alshanqeeti, MD
role: PRINCIPAL_INVESTIGATOR
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