PROTHOR: A randomized controlled trial
Question: The patient has been randomized, later we recognized that he/she does not fulfill the inclusion/exclusion criteria. Is this a dropout?
Answer: No, it is not a dropout, it's a protocol violation. According to the “Intension To Treat” (ITT) principle, the patient has to be treated/investigated as he/she would take par in the study. If the patient has received the study therapy, please describe the situation in the form “Protocol Adherence”. If the patient has not yet received the study therapy he/she should not receive the study therapy (for security reasons). In both cases, the patient should be investigated and followed up as if he/she would participate in the study. In any case, please describe the situation in the form “Protocol Adherence”. (later analysis may include safety but exclude efficiacy issues)
Question: The patient has been randomized, the treating physician did not know that the patient is included in the study. The patient did not receive the study therapy. What should we do now?
Answer:According to the “Intension To Treat” (ITT) principle, the patient has to be treated/investigated as he/she would take par in the study. The patient should be investigated and followed up as if he/she would participate in the study. Please describe the situation in the form “Protocol Adherence”.
Question: The patient has been randomized, received the study therapy and died before reaching the primary endpoint. Is this a drop out?
Answer: No, it's not a dropout. If the patients dies, this is a study result and not a dropout.
Question: The patient has been randomized, received the study therapy and withdrawed his consent. What should we do now?
Answer: Data which has been collected up to the date of consent withdrawal will not be shared, not even in anonymous form and will not be included in the evaluation. This event will be judged as cancellation. It is not a dropout.
Question: The patient has been randomized and received the study therapy. Later we discovered that the patient took part in two interventional studies. What should we do?
Answer: This will be an individual decision. Please report such events to the international study coordinator. If the two trials do not influence each other, the study may be continued. If interference is suspected, one trial has to stop. This event will be judged as dropout. Please note, that one of the exclusion criteria of the PROTHOR trial is “participation in another interventional trial”. The study team may get serious trouble and loose insurancy entitlement if the patient participates in two interventional trials.
Question: The patient has been randomized, received the study therapy and is not reachable for follow up. Is this a dropout?
Answer: If the patient has been randomized and the primary endpoint variable could not be collected, it's a dropout.
Question: If the duration of NIV was 60 hours, should I mark “yes” to “New Requirement of NIV” in post operative day 1 (POD1) and list the duration as 24 hours, mark “yes” to “New Requirement of NIV” in POD2 (list the duration as 24 hours), and then mark “yes” to “New Requirement of NIV” in POD3 (and list the duration as 12 hours)? Or should I simply mark “yes” to “New Requirement of NIV” in POD1 and list the duration as 60 hours?
Answer: Please enter 24 hours to the field POD1, 48 hours to POD2 and 60h to POD3 (cumulative since extubation).
Question: The reexpansion of the non ventilated lung at the end of the surgery, how should it be performed? In the high PEEP group, do I have to perform two recruitment maneuvers (one during OLV, a second with TLV) ?
Answer: Let's make an example for the high PEEP group. The Patient is in lateral position, the surgery is ongoing.. Every one hour during OLV you should perform a recruitment maneuver (please record the recruitment data). At the end of OLV, the surgeon will ask you to reexpand the lung. Now you should reexpand the lung with a CPAP valve (to control the pressure and to obtain standardization among centers. If you don't have a CPAP valve, consider connection of a second ventilator that is able to perform CPAP to the non-ventilated lung)
Now the lung is expanded. You don't have to record the recruitment data of lung reexpansion. As soon as you have reestablished two lung ventilation (typically in lateral position) please perform a recruitment maneuver and record the data (in the database the time point is called “after lung re-expansion, TLV”). After surgery, the patient should be repositioned in supine position. Please perform the recruitment maneuver (timepoint: “at end of surgery (supine)”). Then the patient can be extubated.
For the low PEEP group there are no recruitment maneuvers. For reexpansion of the non-ventilated lung, please perform the CPAP maneuver as described (CPAP valve or second ventilator, stepwise increase of continuous airway pressure up to 20 cmH2O).
An adverse event (AE) is generally defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding) syndrome or disease which either occurs during the study, having been absent at baseline, or if present at baseline, appears to worsen. Adverse events are to be recorded regardless of their relationship to the study intervention.
A Serious Adverse Event is defined as any experience that suggests a significant hazard or any unwanted medical occurrence that:
Investigators should report all Adverse Events, which are related to study procedures within 24 hours to the SAE manager. Also, all serious adverse events regardless of their relationship to the study intervention should be reported to the SAE manager within 24 hours. The SAE manager will then notify the DSMB. The SAE manager is Ary Serpa Neto (firstname.lastname@example.org).
The SAE manager will work collaboratively with the reporting investigator to determine if a serious adverse event has a reasonable possibility of having been caused by the study procedure. The SAE manager will also determine if the event is unexpected. An adverse is considered “unexpected” if it is not expected as a consequence of the study procedure.
The SAE manager will report all unexpected and study related deaths, and SAEs to the DSMB seven days after receipt of the report from a center. A written report will be sent to the DSMB within 15 calendar days. The DSMB will also review all adverse events and clinical outcomes during scheduled interim analyses. If the DSMB determines that the overall rate of adverse events is higher in the study group than the control group the centers will be notified 15 days of this.
Investigators will be asked to grade the strength of the relationship of an adverse event to study procedures as follows: