Clinical trial NCT04386070: Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19
Official title: Preventing Pulmonary Complications in Surgical Patients at Risk of COVID-19
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Pulmonary Complications in Surgical Patients
COVID
Severe Acute Respiratory Syndrome
Keywords: Surgery
Pneumonia
COVID 19
COVID
SARS-Cov-2
SARS
Lead sponsor: University of Birmingham
Sponsor class: OTHER
Collaborators: name: Christian Medical College and Hospital, Ludhiana, India
name: Ministry of Health, Ghana
name: University of Lagos, Nigeria
name: Kigali University Teaching Hospital
name: Hospital Español Veracruz
name: Université d'Abomey-Calavi
name: University of Witwatersrand, South Africa
name: University of Edinburgh
name: Istituto Clinico Humanitas
name: University of Cape Town
First posted: 2020-05-13
Enrollment: 6400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: PREVENTION

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

Eligibility criteria: 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

Primary outcomes:
measure: Pneumonia free survival; acute respiratory distress syndrome (ARDS) free survival; or death
timeFrame: From randomisation until discharge from hospital, average less than 30 days
Secondary outcomes:
measure: Rate of Pneumonia
timeFrame: From randomisation until discharge from hospital, average less than 30 days
measure: Rate of ARDs
timeFrame: From randomisation until discharge from hospital, average less than 30 days
measure: Death rate
timeFrame: From randomisation until discharge from hospital, average less than 30 days
measure: Rate of unexpected ventilation
timeFrame: From operation until 30 days post operation
measure: COVID-19 pulmonary complications
timeFrame: 30 days post-surgery
measure: Duration of hospital stay
timeFrame: 30 days post-surgery
measure: Pulmonary function
timeFrame: 30 days post-surgery
Other outcomes:
Locations:
city: Gwagwalada
country: Nigeria
facility: University Of Abuja Teaching Hospital (Spoke)
city: Lagos
country: Nigeria
facility: Lagos University Teaching Hospital (Hub)
city: Nnewi
country: Nigeria
facility: Nnamdi Azikiwe University Teaching Hospital (Spoke)
city: Butare
country: Rwanda
facility: University Teaching Hospital of Butare (CHUB) (Spoke)
city: Kibungo
country: Rwanda
facility: Kibungo Referral Hospital (Spoke)
city: Kigali
country: Rwanda
facility: Kibagabaga Hospital (Spoke)
city: Kigali
country: Rwanda
facility: University Teaching Hospital of Kigali (Hub)
city: Kirambo
country: Rwanda
facility: Kibogora District Hospital (Spoke)
city: Ruhengeri
country: Rwanda
facility: Ruhengeri Referral Hospital (Spoke)
Study officials:
affiliation: University of Birmingham
name: Aneel Bhangu
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.