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

NCT ID: NCT04386070

Last Updated: 2025-02-20

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE3
• Total Enrollment: 6400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-16
• Study Completion Date: 2027-03-01

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

Conditions

Pulmonary Complications in Surgical Patients; COVID; Severe Acute Respiratory Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Control (normal practice)

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

RESP301

Intervention Type: DRUG

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.

Interventions

RESP301

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Christian Medical College and Hospital, Ludhiana, India

OTHER

Sponsor Role: collaborator

Ministry of Health, Ghana

OTHER_GOV

Sponsor Role: collaborator

University of Lagos, Nigeria

OTHER

Sponsor Role: collaborator

Kigali University Teaching Hospital

OTHER

Sponsor Role: collaborator

Hospital Español Veracruz

UNKNOWN

Sponsor Role: collaborator

Université d'Abomey-Calavi

OTHER

Sponsor Role: collaborator

University of Witwatersrand, South Africa

OTHER

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: collaborator

Istituto Clinico Humanitas

OTHER

Sponsor Role: collaborator

University of Cape Town

OTHER

Sponsor Role: collaborator

University of Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aneel Bhangu

Role: PRINCIPAL_INVESTIGATOR

University of Birmingham

Locations

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

Countries

Nigeria; Rwanda

References

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.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

Other Identifiers

2020-001448-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RG_20-029 COVID-19

Identifier Type: -

Identifier Source: org_study_id