Effectiveness of Ammonium Chloride in Reducing Viral Load (ACTEarly)

National and Kapodistrian University of Athens

Status: Completed

Conditions: Viral Infection COVID-19; Influenza A and B; RNA Virus Infections

Study type: Observational

Funder types: Other

Identifiers

NCT07254052

Sotiria GH 14328/17-05-2025

Details and patient eligibility

About

This is a prospective, double-blind, randomized, comparative effectiveness pilot study evaluating the effect of a sustained-release ammonium chloride formulation (ACF) on viral load dynamics in adult patients with mild or moderate COVID-19 or seasonal influenza infection.

Eligible participants are randomly assigned in a 1:1 ratio to receive either ACF (ammonium chloride with vitamin D) or a control formulation (vitamin D only) twice daily for 10 consecutive days. The primary objective is to assess the reduction of viral load measured by RT-PCR cycle threshold (Ct) values at baseline, Day 3-5, and Day 10-12. Secondary objectives include the duration and severity of symptoms, incidence of hospitalization, oxygen supplementation, ICU admission, and mortality.

The study is conducted in both inpatient and outpatient settings at Sotiria General Hospital for Chest Diseases, Athens, Greece as well as at the outpatient clinic "En Ygeia". All viral load analyses are performed at the Department of Pharmacy, National and Kapodistrian University of Athens. A total of 32 participants were enrolled. This study aims to generate early clinical evidence regarding the antiviral effectiveness of ACF as an adjunct strategy in respiratory RNA virus infections.

Full description

This is a prospective, double-blind, randomized, comparative effectiveness pilot clinical study designed to evaluate the antiviral effect of a sustained-release ammonium chloride formulation (ACF) in adult patients with mild or moderate SARS-CoV-2 or seasonal influenza infection. Respiratory viral infections remain a major global health burden, and safe, accessible adjunct therapies are needed to complement existing public health measures and vaccination strategies.

Eligible participants are adults (≥18 years) with a positive rapid test for SARS-CoV-2 or influenza A/B, recruited at the Outpatients Clinic or Emergency Department of Sotiria General Hospital for Chest Diseases and at "En Ygeia" outpatient clinic. Participants are randomized in a 1:1 ratio to receive either:

1. ACF (nutritional supplement): sustained-release ammonium chloride formulation with vitamin D, one capsule every 12 hours for 10 days
2. VDF (control): matched sustained-release placebo formulation containing only vitamin D, one capsule every 12 hours for 10 days.

Both inpatients and outpatients are included. Exclusion criteria are: age <18 years, pregnancy or lactation, denial of informed consent, known allergy to study components, organ transplantation, and frailty score ≥5. Participants may discontinue the study in cases of intolerance, non-compliance, or withdrawal of consent.

The primary endpoint is the reduction of viral load, assessed through RT-PCR cycle threshold (Ct) values obtained at baseline (Day 1), Day 3-5, and Day 10-12.

Secondary endpoints include:

• Duration and severity of symptoms for 30 days
• Incidence of hospitalization (for outpatients)
• Need for oxygen supplementation
• ICU admission
• Intubation
• Death. All RT-PCR testing for SARS-CoV-2 and influenza A/B were performed at the Department of Pharmacy, National and Kapodistrian University of Athens. The study employs standardized sampling, nucleic acid extraction, and real-time PCR quantification with certified reference materials.

Statistical analysis compared Ct values across timepoints within and between groups. Mean percentage change in Ct values was compared using appropriate parametric or non-parametric tests, with additional analyses for secondary outcomes. The final sample size was 32 patients.

This pilot trial aims to provide early clinical evidence regarding the potential antiviral effectiveness of ammonium chloride in the context of mild respiratory viral infections, contributing to the design of larger confirmatory studies.

Enrollment: 32 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults ≥ 18 years.
• Positive rapid test for Sars-CoV-2 19 or influenza (performed at the Outpatients Clinic or the Emergency Department).
• Informed consent.

Exclusion criteria

• Age < 18 years.
• Pregnancy, and/or lactation.
• Denial of Informed Consent.
• Known allergy to ammonium chloride or to any of the ACF, or VDF excipients.
• Organ transplantation.
• Frailty score ≥ 5.

Trial design

32 participants in 2 patient groups

ACF receiving participants

Description:

Participants assigned to this group received the sustained-release ammonium chloride formulation (ACF), containing 500 mg ammonium chloride and 2,000 IU vitamin D per capsule. One capsule was administered orally every 12 hours for 10 consecutive days, starting on Day 1. Both inpatients and outpatients with mild or moderate COVID-19 or seasonal influenza infection were included. The intervention aimed to evaluate the effect of ammonium chloride on viral load reduction and clinical outcomes compared to the control group. Randomization and double-blinding were maintained throughout the study.

Control Group (VDF receiving participants)

Description:

Participants assigned to this group received the control formulation consisting of sustained-release tablets containing 2,000 IU vitamin D and identical excipients, but no ammonium chloride. One capsule was administered orally every 12 hours for 10 consecutive days, starting on Day 1. Both inpatients and outpatients with mild or moderate COVID-19 or seasonal influenza infection were included. This control arm was used to compare changes in viral load dynamics and clinical outcomes against the intervention group. Randomization and double-blinding were maintained throughout the study.