A clinical trial to evaluate the effects of inhaled nitric oxide gas among COVID-19 patients with pneumonia
| ISRCTN | ISRCTN16806663 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16806663 |
- Submission date
- 09/03/2021
- Registration date
- 11/03/2021
- Last edited
- 11/08/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe. In some patients, this can progress to respiratory failure and patients may need supplemental oxygen or in severe cases, ventilator support to maintain normal oxygen levels. The death rate in patients who need mechanical ventilation to maintain oxygenation is quite high, additionally, ventilator support can lead to secondary infections and expensive healthcare costs.
Effective antivirals that could combat COVID-19 are currently unavailable. Research studies have reported the antiviral and antimicrobial activity of Nitric oxide against pathogens. It can also provide better oxygenation by widening of blood vessels (vasodilation). This trial will explore the effect of inhaled nitric oxide on clinical improvement among patients diagnosed with COVID-19 pneumonia.
Who can participate?
Adult COVID-19 pneumonia patients with respiratory failure due to inability for maintaining appropriate oxygen levels in the blood.
What does the study involve?
Eligible COVID-19 patients will be recruited into the study. Participants will be allocated to one of two groups, with an equal chance of being in either group (like tossing a coin). Participants and researchers will not have a choice in the treatment given. One group will receive standard care only and the other group will receive Inhaled Nitric Oxide using a helmet or tight sealing mask, as pulses lasting for 30 minutes at 12-hour intervals, for 3 consecutive days.
Trained research staff will collect the clinical information of each patient and nasal swabs will be collected on days 3, 5, 7, 10, and 14 post-treatment to estimate the quantity of virus (viral load).
What are the possible benefits and risks of participating?
At the time of writing, there are no proven therapies for this viral disease and if the study drug is effective it could potentially shorten the course and/or severity of the disease in patients. There are no known risks due to study participation.
Where is the study run from?
Amrita Institute of Medical Sciences (India)
When is the study starting and how long is it expected to run for?
From June 2020 to February 2021
Who is funding the study?
Amrita School of Biotechnology (India)
Who is the main contact?
Dr Aveek Jayant, jayant.aveek@gmail.com
Contact information
Public
Department of Cardiac Anaesthesia
Amrita Institute of Medical Sciences
AIMS P.O
Kerala
Kochi
682041
India
 ORCID ID |
0000-0002-3465-1229 |
|---|---|
| Phone | +91-484-2851234 |
| jayant.aveek@gmail.com |
Scientific
Department of General Medicine and Division of Infectious Diseases
Amrita Institute of Medical Sciences
AIMS P.O
Kerala
Kochi
682041
India
| Phone | +91-484-2852250 |
|---|---|
| drmerlin.blessan@gmail.com |
Study information
| Study design | Prospective phase II open-label randomized controlled feasibility trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | See additional files |
| Scientific title | A phase II open-label, randomized, controlled feasibility trial to compare the antiviral activity and clinical efficacy of inhaled nitric oxide gas among COVID-19 patients diagnosed with pneumonia with hypoxic respiratory failure |
| Study objectives | Nitric oxide increases antiviral activity and reduces hypoxic damage by improved oxygenation. |
| Ethics approval(s) | Approved 08/05/2020, Institutional Ethics Committee Amrita Institute of Medical Sciences (AIMS, Ponekkara, Kochi, Edappally, Ernakulam, Kerala 682041, India; +91 (0)484 2858750; https://www.amritahospitals.org/), ref: IEC/AIMS-2020/CARDANES-044 |
| Health condition(s) or problem(s) studied | Adult COVID-19 pneumonia patients with hypoxic respiratory failure |
| Intervention | Eligible patients will be randomized into two arms either receiving standard of care only (control arm), or standard of care and inhaled Nitric Oxide (iNO) using a helmet or tight sealing oronasal mask (case arm). iNO will be deluvered as pulses lasting for 30 min at 12 h intervals, for 3 consecutive days. iNO will be administered at the minimum FiO2 to maintain saturations above 92%, using a V60 bilevel positive airway pressure (BiPAP) machine. The flow rates will be titrated to administer escalating doses of iNO starting from 10 ppm to 80 ppm over a period of 30 min. Following this iNO will be weaned off at the rate of 10 ppm per min. Study patients will be started on oral Sildenafil 10 mg TID for 5 days, to prevent rebound rise in pulmonary pressures after iNO discontinuation, provided their MAP is >60 mmHg. Standard of care therapies including antivirals, steroids, anticoagulants, and other medications will be administered in both study arms as per institutional protocol. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Nitric Oxide gas |
| Primary outcome measure | Viral load as defined by cycle threshold measured using Real-Time Polymerase Chain Reaction Surrogate CT ratio from nasopharyngeal swab collected at baseline 3, 5, 7, 10, and 14 days |
| Secondary outcome measures | 1. Duration of non-invasive ventilation (NIV) measured from the nursing chart and medical record evaluation recorded at 8 am and 8 pm daily by investigators during the study period collected at end of NIV 2. Duration of oxygen therapy measured from the nursing chart and medical record evaluation recorded at 8 am and 8 pm daily by investigators during the study period collected at end of oxygen therapy 3. Methaemoglobin levels measured using arterial blood gas analysis using a co- oximeter RADIOMETER ABL 800 on blood gas samples drawn after each pulse of iNO therapy at baseline, 1, 2, and 3 days 4. Incidence of methaemoglobin levels >3% during the trial measured using arterial blood gas analysis using a co- oximeter RADIOMETER ABL 800 on blood gas samples drawn after each pulse of iNO therapy at baseline, 1, 2, and 3 days 5. Severe acute respiratory infection (SARI) scale performance assessed during daily rounds by the clinical team collected daily until ICU discharge or achievement of the lowest numeric, whichever is earlier 6. Patient status measured using the Sequential Organ Failure Assessment (SOFA) score from medical chart/investigations obtained at 8 am at baseline and 72 h 7. Length of hospital stay measured from medical chart review on the day of hospital discharge 8. Length of intensive care unit (ICU) stay measured from medical chart review on the day of ICU discharge 9. Deaths measured by investigators for all patients in each arm and followed up daily recorded on the day of death or the immediate day after |
| Overall study start date | 10/06/2020 |
| Completion date | 05/02/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 25 |
| Total final enrolment | 29 |
| Key inclusion criteria | 1. Severe acute respiratory infection (SARI) class 4 and 5 (hospitalized with the requirement of oxygen supplementation, high flow oxygen device, or non-invasive ventilation assistance) 2. Respiratory rates <30 and saturating >90% with oxygen or Non-Invasive Ventilation (NIV) |
| Key exclusion criteria | 1. Mental obtundation at ICU admission 2. Contraindications or unwillingness to NIV 3. Requiring mechanical ventilation at ICU admission 4. Pre-enrollment diagnosis of chronic renal failure (CRF) or stage 1 Acute Kidney Injury (AKI) as per Kidney Disease Improving Global Outcomes (KDIGO) guidelines 5. Presence of hemoglobinopathies 6. Shock at presentation (mean arterial pressure <60) 7. History of G6PD deficiency or baseline methemoglobin >3% 8. Presence of baseline pulmonary artery hypertension 9. Pregnancy or breastfeeding |
| Date of first enrolment | 20/09/2020 |
| Date of final enrolment | 12/12/2020 |
Locations
Countries of recruitment
- India
Study participating centre
Ponekkara
Kochi
682041
India
Sponsor information
Hospital/treatment centre
AIMS P.O
Ponekkara
Kochi
682041
India
| Phone | +91 484 285 1234 |
|---|---|
| md@aims.amrita.edu | |
| Website | http://www.amritahospitals.org/ |
"ROR" |
https://ror.org/05ahcwz21 |
Funders
Funder type
University/education
No information available
Results and Publications
| Intention to publish date | 05/02/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned for publication in a high-impact peer-reviewed journal. The full trial record (methods statistical plan and results) will be uploaded post-completion either as part of the trial record or on a registry of peer prints such as medrxiv.org. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 31/03/2022 | 11/08/2022 | Yes | No |
Editorial Notes
11/08/2022: Publication reference added.
19/03/2021: Internal review.
11/03/2021: Trial’s existence confirmed by Institutional Ethics Committee Amrita Institute of Medical Sciences.
