The effect of surfactant on clinical outcome of patients with COVID-19 under mechanical ventilation: A structured summary of a study protocol for a randomised controlled trial

Objectives Assessing the effect of surfactant on clinical outcome in patients with COVID-19 under mechanical ventilation Trial design Single centre, two arm, parallel group (1:1 allocation ratio), randomised superiority trial with blinded care and outcome assessment. Participants Inclusion criteria: Adult COVID-19 patients admitted to the ICU in Modarres hospital, Tehran, Iran (age range of 18 to 99 years) with moderate to severe ARDS (based on definition of P/F ratio) requiring auxiliary respiratory devices (either intubation or face mask). Exclusion criteria: ● Existence of a major underlying pulmonary disease in addition to COVID-19 ● Underlying congenital heart disease ● Patients needing extracorporeal membrane oxygenation (ECMO) ● ARDS primarily due to any other reason rather than COVID-19 ● The primary source of pulmonary involvement was bacterial pneumonia or any other etiology except for COVID-10 induced lung involvement ● Those who refused to continue the study (either the patient or their family) ● any patient had any sign of healing before entering the study leading to discharge from ICU in less than 12 hours Intervention and comparator In the intervention group, the dose of the drug is a vial containing 4 ml, equivalent to 100 mg, which is prescribed for an adult weighing about 70 kg each time, and if the patient's weight is much lower or higher, it will be adjusted accordingly. Surfactant is prescribed inside the trachea in two doses, starting on the day of intubation with a second dose 6 hours later. The control group will receive the same volume of normal saline, based on weight, administered into the trachea with the same time schedule. Main outcomes 30 days mortality; patient mortality during stay in ICU up to 30 days; ICU length of stay up to 30 days; Time under mechanical ventilation up to 30 days. Randomisation After the participant enters the study, i.e. after the qualification of the patients in the trial is confirmed and their informed written consent is taken, we will use a simple randomisation method using a table of random numbers. In order to hide the random allocation process, a central randomisation approach will be used and the random sequence will be at the disposal of one of the researchers, excluding the principal investigator. Blinding (masking) Participants, healthcare providers and the principal investigator assessing the outcomes will all be blinded to the group assignment. Numbers to be randomised (sample size) A total of 60 participants will be randomised in a 1:1 allocation ratio (30 patients allocated to the intervention group and 30 patients allocated to the control group). Trial Status The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. Trial registration IRCT registration number: IRCT20091201002804N12 Registration date: 1st June 2020, 1399/03/12 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information Supplementary information accompanies this paper at 10.1186/s13063-020-04815-z.


Study aim
Assessing the effect of surfactant on clinical outcome in patients with Covid-19 under mechanical ventilation

Design
Two arm parallel group randomized trial with blinded care and outcome assessment

Settings and conduct
COVID-19 patients under mechanical ventilation would enter the study; one group would receive the standard treatment added with placebo and the other group would receive standard care plus intra-tracheal surfactant

Participants/Inclusion and exclusion criteria
Inclusion criteria: If the patient is intubated and under mechanical ventilation with SpO2<85% If the patient has confirmed COVID-19 Exclusion criteria: Existence of a major underlying pulmonary disease in addition to COVID-19 Underlying congenital heart disease

Intervention groups
In the intervention group, based on the dose announced in the study protocol, surfactant is prescribed inside the trachea in two doses at a distance of 6 hours, and at the same time, the dependent variables of the study are measured. At the same time, in the control group, the same volume of normal saline is administered in the trachea within the same time schedule

Participant
Care provider Investigator

Sample size
Target sample size: 60

Randomization description
After the participant enters the study, i.e. after the qualification of the patients in the trial is confirmed and their informed written consent is taken, simple randomization will be done as follows: 1-Table of random numbers will be used for creation of coincidence of random allocation. 2-In order to hide the random allocation process, the central randomization approach will be used, while the random sequence would be at the disposal of one of the researchers except for the principal investigator.

Blinding description
participants after entering the study would not know whether they are in the drug or placebo group healthcare providers (Physicians and nurses) would administer the prepared vial including drug or placebo while they do not know its content; the vial would be assimilated; regardless of drug or placebo principle investigator does not know whether the patient belongs to the drug group or the placebo group since the patients have been randomized Health conditions studied 1

Description
Intervention group: Intra-tracheal surfactant in COVID-19 patients who are under mechanical ventilation, which includes the administration of a standard dose of surfactant inside the airway of the patient with COVID-19 diagnosis, which is administered immediately on the first day of intubation and in two doses at intervals within 6 hours. The dose of the drug is a vial containing 4 ml, equivalent to 100 mg, which is prescribed for an adult weighing about 70 kg each time, and if the patient's weight is higher, it will be adjusted accordingly. The drug is from the brand Beraksurf® and is supplied by Tekzima. Sharing plan

Deidentified Individual Participant Data Set (IPD)
Yes -There is a plan to make this available

Study Protocol
Yes -There is a plan to make this available

Statistical Analysis Plan
Yes -There is a plan to make this available

Informed Consent Form
Yes -There is a plan to make this available

Clinical Study Report
Yes -There is a plan to make this available

Analytic Code
Yes -There is a plan to make this available

Data Dictionary
Yes -There is a plan to make this available Title and more details about the data/document all collected deidentified IPD When the data will become available and for how long starting in January 2022 To whom data/document is available the data would be available for people working in academic institutions and people working in businesses Under which criteria data/document could be used Email alidabbagh@yahoo.com