Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19

Phase 3

Suspended

• Conditions: COVID; Pulmonary Complications in Surgical Patients; Severe Acute Respiratory Syndrome
• Interventions: Drug: RESP301

• Registration Number: NCT04386070
• Lead Sponsor: University of Birmingham

Brief 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)

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:

A. 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 Timeline

• Study First Submitted: 2020-04-30
• Study First Submitted QC: 2020-05-12
• Study First Posted: 2020-05-13
• Study Start: 2022-05-16
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-18
• Last Update Posted: 2025-02-20
• Primary Completion: 2026-12-31
• Study Completion: 2027-03-01

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 6400

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RESP301	RESP301	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.

Primary Outcome Measures

Name	Time	Method
Pneumonia free survival; acute respiratory distress syndrome (ARDS) free survival; or death	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

Secondary Outcome Measures

Name	Time	Method
Duration of hospital stay	30 days post-surgery	Duration of hospital stay (including time spent in intensive care, time ventilated)
Pulmonary function	30 days post-surgery	Pulmonary function in keeping with the World Health Organisation (WHO) Solidarity Trial outcome scale
Rate of ARDs	From randomisation until discharge from hospital, average less than 30 days	ARDs will be presented and analysed separately as a secondary outcome measure
Rate of Pneumonia	From randomisation until discharge from hospital, average less than 30 days	Pneumonia will be presented and analysed separately as a secondary outcome measure as well as within the composite primary outcome measure.
Death rate	From randomisation until discharge from hospital, average less than 30 days	Death will be presented and analysed separately as a secondary outcome measure
Rate of unexpected ventilation	From operation until 30 days post operation	Unexpected inability to extubate and wean patient from ventilation after general anaesthesia, or reintubation and ventilation by 30 days after surgery
COVID-19 pulmonary complications	30 days post-surgery	Postoperative diagnosis of proven COVID-19 pulmonary complications

Trial Locations

Locations (9)

University Of Abuja Teaching Hospital (Spoke); 🇳🇬 Gwagwalada, Nigeria

Lagos University Teaching Hospital (Hub); 🇳🇬 Lagos, Nigeria

Nnamdi Azikiwe University Teaching Hospital (Spoke); 🇳🇬 Nnewi, Nigeria

University Teaching Hospital of Butare (CHUB) (Spoke); 🇷🇼 Butare, Rwanda

Kibungo Referral Hospital (Spoke); 🇷🇼 Kibungo, Rwanda

Kibagabaga Hospital (Spoke); 🇷🇼 Kigali, Rwanda

University Teaching Hospital of Kigali (Hub); 🇷🇼 Kigali, Rwanda

Kibogora District Hospital (Spoke); 🇷🇼 Kirambo, Rwanda

Ruhengeri Referral Hospital (Spoke); 🇷🇼 Ruhengeri, Rwanda