Pulmonary Complications in Surgical PatientsPhase 3PROTECT-SurgNCT04386070
Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19
A Phase 3 study testing RESP301 in people with Pulmonary Complications in Surgical Patients and COVID, run by University of Birmingham at 9 sites in 2 countries.
Trial summary
The aim of this study is to reduce pulmonary complications in adult patients undergoing abdominal or thoracic surgery in COVID-19 exposed hospital environments. A Trial in Low and Middle Income Countries (LMICs) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Complications in Surgical Patients, COVID, Severe Acute Respiratory Syndrome
- What is being tested?
- RESP301
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6,400 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 16 May 2022to 1 Mar 2027
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18 years and over. (This criteria MUST be made country-specific)
- Planned to undergo abdominal or thoracic elective or emergency inpatient surgery requiring general anaesthesia.
- Asymptomatic of COVID-19, including patients with: those not tested, negative test results, positive test but no symptoms (to be monitored post-surgery for symptoms)
- Informed patient consent.
- Able to operate a vibrating mesh nebuliser, as assessed by the recruiting physician
Who cannot join
- Procedures under local anaesthesia
- Known history of adverse reaction/contraindication to trial drug
- Pregnancy and/or lactating patients (including patients undergoing caesarean section)
- History of methaemoglobinaemia
- Patients receiving any type of prescribed nitric oxide-donating agents (e.g. Nitroprusside, Isosorbide dinitrate, Isosorbide mononitrate, Naproxcinod, Molsidomine and Linsidomine)
- Unable to tolerate use of a nebuliser and/or deemed unlikely to be able to adhere to protocol in view of investigator
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
Rwanda6 sites
University Teaching Hospital of Butare (CHUB) (Spoke)
Butare
Kibungo Referral Hospital (Spoke)
Kibungo
Kibagabaga Hospital (Spoke)
Kigali
University Teaching Hospital of Kigali (Hub)
Kigali
Kibogora District Hospital (Spoke)
Kirambo
Ruhengeri Referral Hospital (Spoke)
Ruhengeri
Nigeria3 sites
University Of Abuja Teaching Hospital (Spoke)
Gwagwalada, 902101
Lagos University Teaching Hospital (Hub)
Lagos
Nnamdi Azikiwe University Teaching Hospital (Spoke)
Nnewi, 435101
About this study
The aim of this study is to reduce pulmonary complications in adult patients undergoing abdominal or thoracic surgery in COVID-19 exposed hospital environments. A Trial in Low and Middle Income Countries (LMICs)
Read the detailed description
This trial has an adaptive platform design to identify at the earliest opportunity intervention arms which are showing benefit, drop arms which have a clear lack of benefit, and rapidly introduce new therapeutic options to the platform. This will enable rapid feedback of results to clinicians, allowing the standard of care to be modified as the pandemic progresses. Regular and frequent monitoring of results will be guided by an experienced, independent DMC.
Eligible patients will be randomised at the level of the individual in a 1:1 ratio between:
- Control (normal practice) B. RESP301 6ml mixture of 150mM sodium nitrate, 50mM mannitol and 100mM citric acid, buffered at pH 5.4, three times per day (at least 4 hours apart), for 7 days or until discharge, whichever occurs first
- Being tested
- RESP301
- Keywords
- Surgery, Pneumonia, COVID 19, COVID, SARS-Cov-2, SARS
- Medical subject headings
- Severe Acute Respiratory Syndrome, Pneumonia, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RESP301Drug
RESP301 is a formulation consisting of three agents already used in clinical practice: mannitol, sodium nitrite and citric acid. Delivered by a vibrating mesh nebuliser three times per day (TID) (at least 4 hours apart), for 7 days. Each dose of RESP301 is a 6ml admixture of 150mM NaNO2, 50mM mannitol and 100mM citric acid, buffered at pH 5.4.
| Study group | Role | What they receive |
|---|---|---|
| Control (normal practice) | No intervention | Treatment without the trial intervention. Patients will be treated as per hospital routine practice. The control arm may change over the course of the trial and will be monitored by the TMG and DMC |
| RESP301 | Experimental | RESP301 is administered quickly (8-10 minutes) via an easy-to-use, vibrating mesh nebuliser. The recommended nebulisers used to administer this intervention are available in all participating countries. The intervention will be administered using a nebuliser according to standard local practice; where permitted for patients to self-administer, a member of the clinical team will ensure that the patient has viewed the intervention administration training video, and will also oversee the patient for the first trial dose to ensure proper administration. Receives: Drug: RESP301 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pneumonia free survival; acute respiratory distress syndrome (ARDS) free survival; or death
The primary outcome is any one of the following, inpatient, postoperative pulmonary complications:
Pneumonia Acute respiratory distress syndrome (ARDS) Death
Measured: From randomisation until discharge from hospital, average less than 30 days
Secondary outcomes (7)
Rate of Pneumonia
Pneumonia will be presented and analysed separately as a secondary outcome measure as well as within the composite primary outcome measure.
Measured: From randomisation until discharge from hospital, average less than 30 days
Rate of ARDs
ARDs will be presented and analysed separately as a secondary outcome measure
Measured: From randomisation until discharge from hospital, average less than 30 days
Death rate
Death will be presented and analysed separately as a secondary outcome measure
Measured: From randomisation until discharge from hospital, average less than 30 days
Rate of unexpected ventilation
Unexpected inability to extubate and wean patient from ventilation after general anaesthesia, or reintubation and ventilation by 30 days after surgery
Measured: From operation until 30 days post operation
COVID-19 pulmonary complications
Postoperative diagnosis of proven COVID-19 pulmonary complications
Measured: 30 days post-surgery
Duration of hospital stay
Duration of hospital stay (including time spent in intensive care, time ventilated)
Measured: 30 days post-surgery
Pulmonary function
Pulmonary function in keeping with the World Health Organisation (WHO) Solidarity Trial outcome scale
Measured: 30 days post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2020
- Study start16 May 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion1 Mar 2027 (estimated)
Why it stopped: Lack of IMP availability - may resume.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Complications in Surgical PatientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The trial uses a Bayesian adaptive platform design, allowing for termination of arms if their superiority to standard care is established, and addition of new treatment arms. Patients will be randomised 1:1 to (A) Control (normal practice), (B) RESP301
- Masking
- None (open label)
- Enrolment
- 6,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Christian Medical College and Hospital, Ludhiana, India, Ministry of Health, Ghana, University of Lagos, Nigeria, Kigali University Teaching Hospital, Hospital Español Veracruz, Université d'Abomey-Calavi, University of Witwatersrand, South Africa, University of Edinburgh, Istituto Clinico Humanitas, University of Cape Town
- Responsible party
- Sponsor
- Investigators
- Aneel Bhangu, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04386070
- Sponsor's protocol ID
- RG_20-029 COVID-19
- Other IDs
- 2020-001448-24
- Acronym
- PROTECT-Surg
- Status last verified
- Feb 2025
- First submitted
- 30 Apr 2020
- Last updated
- 20 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Hospital-level data will not be released or published. Country-level analyses will only be conducted with permission of lead investigators from each participating country. Local investigators may access their data across their country to perform country-level analyses (all participating hospitals should consent to their data being used in this way).
Publications
Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PubMed 34473343
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19
- ClinicalTrials.gov ID
- NCT04386070
- Acronym / sponsor ID
- PROTECT-Surg / RG_20-029 COVID-19
- Keywords
- Surgery, Pneumonia, COVID 19, COVID, SARS-Cov-2, SARS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Lack of IMP availability - may resume.
- Enrolment
- 6,400 participants (estimated)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- Christian Medical College and Hospital, Ludhiana, India, Ministry of Health, Ghana, University of Lagos, Nigeria, Kigali University Teaching Hospital, Hospital Español Veracruz, Université d'Abomey-Calavi, University of Witwatersrand, South Africa, University of Edinburgh, Istituto Clinico Humanitas, University of Cape Town
- Study start
- 16 May 2022 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 13 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to reduce pulmonary complications in adult patients undergoing abdominal or thoracic surgery in COVID-19 exposed hospital environments. A Trial in Low and Middle Income Countries (LMICs)
Detailed description
This trial has an adaptive platform design to identify at the earliest opportunity intervention arms which are showing benefit, drop arms which have a clear lack of benefit, and rapidly introduce new therapeutic options to the platform. This will enable rapid feedback of results to clinicians, allowing the standard of care to be modified as the pandemic progresses. Regular and frequent monitoring of results will be guided by an experienced, independent DMC.
Eligible patients will be randomised at the level of the individual in a 1:1 ratio between:
- Control (normal practice) B. RESP301 6ml mixture of 150mM sodium nitrate, 50mM mannitol and 100mM citric acid, buffered at pH 5.4, three times per day (at least 4 hours apart), for 7 days or until discharge, whichever occurs first
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The trial uses a Bayesian adaptive platform design, allowing for termination of arms if their superiority to standard care is established, and addition of new treatment arms. Patients will be randomised 1:1 to (A) Control (normal practice), (B) RESP301
| Arm | Type | Receives |
|---|---|---|
| Control (normal practice) | No intervention | –Treatment without the trial intervention. Patients will be treated as per hospital routine practice. The control arm may change over the course of the trial and will be monitored by the TMG and DMC |
| RESP301 | Experimental | Drug: RESP301RESP301 is administered quickly (8-10 minutes) via an easy-to-use, vibrating mesh nebuliser. The recommended nebulisers used to administer this intervention are available in all participating countries. The intervention will be administered using a nebuliser according to standard local practice; where permitted for patients to self-administer, a member of the clinical team will ensure that the patient has viewed the intervention administration training video, and will also oversee the patient for the first trial dose to ensure proper administration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients aged 18 years and over. (This criteria MUST be made country-specific)
- Planned to undergo abdominal or thoracic elective or emergency inpatient surgery requiring general anaesthesia.
- Asymptomatic of COVID-19, including patients with: those not tested, negative test results, positive test but no symptoms (to be monitored post-surgery for symptoms)
- Informed patient consent.
- Able to operate a vibrating mesh nebuliser, as assessed by the recruiting physician
Key exclusion criteria (6 listed)
- Procedures under local anaesthesia
- Known history of adverse reaction/contraindication to trial drug
- Pregnancy and/or lactating patients (including patients undergoing caesarean section)
- History of methaemoglobinaemia
- Patients receiving any type of prescribed nitric oxide-donating agents (e.g. Nitroprusside, Isosorbide dinitrate, Isosorbide mononitrate, Naproxcinod, Molsidomine and Linsidomine)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RESP301RESP301 is a formulation consisting of three agents already used in clinical practice: mannitol, sodium nitrite and citric acid. Delivered by a vibrating mesh nebuliser three times per day (TID) (at least 4 hours apart), for 7 days. Each dose of RESP301 is a 6ml admixture of 150mM NaNO2, 50mM mannitol and 100mM citric acid, buffered at pH 5.4. | Drug | RESP301 |
Primary outcome
Pneumonia free survival; acute respiratory distress syndrome (ARDS) free survival; or death
Time frame: From randomisation until discharge from hospital, average less than 30 days
The primary outcome is any one of the following, inpatient, postoperative pulmonary complications: Pneumonia Acute respiratory distress syndrome (ARDS) Death
7 secondary outcomes
Rate of Pneumonia
Time frame: From randomisation until discharge from hospital, average less than 30 days
Rate of ARDs
Time frame: From randomisation until discharge from hospital, average less than 30 days
Death rate
Time frame: From randomisation until discharge from hospital, average less than 30 days
Rate of unexpected ventilation
Time frame: From operation until 30 days post operation
COVID-19 pulmonary complications
Time frame: 30 days post-surgery
Duration of hospital stay
Time frame: 30 days post-surgery
Pulmonary function
Time frame: 30 days post-surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2025.
- Derived from this study: PubMed 34473343Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
- Individual participant dataSharing planned: No. Hospital-level data will not be released or published. Country-level analyses will only be conducted with permission of lead investigators from each participating country. Local investigators may access their data across their country to perform country-level analyses (all participating hospitals should consent to their data being used in this way).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aneel Bhangu principal investigator
University of Birmingham
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RESP301 in people with Pulmonary Complications in Surgical Patients and COVID, run by University of Birmingham at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 20 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Rwanda, Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pneumonia free survival; acute respiratory distress syndrome (ARDS) free survival; or death (time frame: From randomisation until discharge from hospital, average less than 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04386070, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2025; AzTrials last refreshed its copy on 8 Nov 2026.