Emergency SurgeryTIMENCT04811755
Is TIme From adMission to surgEry an Independent Prognostic Factor for Survival of Patients With Gastro-intestinal Perforation Associated With Septic Shock: (TIME) An Italian Intersocietary Retrospective and Prospective Observational Trial
An observational study of Emergency Surgery, run by San Luigi Gonzaga Hospital.
Trial summary
Gastro-intestinal perforation is a condition that can become life-threatening in case of appearance of systemic symptoms, sepsis-related peripheral hypoperfusion and single or multiple organ failure needing a prompt intervention in Emergency Department (ED) setting. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Emergency Surgery
- What is being tested?
- Surgical timing from ED admission to surgery
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 3,276 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2009to 31 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients undergoing emergency surgery for gastro-intestinal perforations, with or without signs of septic shock
Who may be able to join
- more than 18 years old
- emergency surgery for gastro-intestinal perforations
- with or without signs of septic shock
Who cannot join
- All patients with covered perforations or abdominal perivisceral free air bubbles treated with non- operative management
- delayed surgery
About this study
Gastro-intestinal perforation is a condition that can become life-threatening in case of appearance of systemic symptoms, sepsis-related peripheral hypoperfusion and single or multiple organ failure needing a prompt intervention in Emergency Department (ED) setting. Literature reports disagreeing data about the effect of surgical timing on mortality and postoperative outcomes: Buck et al. described a 2.4 % of decreased survival every hour of surgical delay in case of perforated peptic ulcers. Other authors documented significantly longer postoperative hospital stay, greater health costs and a significant increase of postoperative complication and mortality rates when surgery is delayed in high-risk patients with comorbidities or age > 65 years. Azuhata described a highly significant relationship between delayed surgery and patients' survival: after 6 hours from admission to ED, patients with gastrointestinal perforation and associated septic shock don't survive to surgery. The aim of this study is to assess the impact of delay of time between patient admission to ED and surgery for source control on 30-d mortality and postoperative outcomes in patients with gastrointestinal perforation with or without septic shock. Furthermore, we want to define the time threshold within which surgery can affect patients' survival.
Read the detailed description
This is an Italian National multicenter study composed by a retrospective phase of data collection from patients of past ten years and a perspective one of next two years.
INCLUSION AND EXCLUSION CRITERIA We include in our analysis all patients with more than 18 years old undergoing emergency surgery for gastro-intestinal perforations, with or without signs of septic shock. All patients with covered perforations or abdominal perivisceral free air bubbles treated with non- operative management or delayed surgery will be excluded. An online Case Report Form (CRF) will be filled out by every participating Italian participating center.
ENDPOINTS Primary outcome analyzed is in-hospital Clavien-Dindo > 3 complication rate [12]. Secondary outcomes are 60-d mortality rate, total length of stay (LOS), LOS in Intensive Care Unit (ICU), days of mechanical ventilation, re-intervention rate and 30-d readmission rate.
Analyzed variables are:
- Hospital characteristics; teaching/non-teaching setting; I/II level ED; emergency surgery/volume x year; 24H/on-call radiology and surgery team; presence of a dedicated OR in ED;
- Patient demographics (gender, age, Body Mass Index (BMI) and American Society of Anaesthesiologists' (ASA) classification of Physical Health, medical history of past abdominal surgical operations and comorbidities according to Charlson Comorbidity Index (CCI), mainly related to corticosteroids therapy and immunosuppressive conditions),
- Patient management in ED: admission date and time; Priority code at admission; time of abdominal x-Ray; time of CT-scan; Time of patient evaluation by surgeon on- call; Preoperative resuscitation management (Y/N, type, time of beginning); presence of Sepsis (infection documented or suspected + SOFA >=2) and of septic shock (sepsis + persistent hypotension needing vasopressors to maintain a Mean Arterial Pressure (MAP) of 65 mmHg; serum values of lactates > 18 mg/dL (or 2 mmol/L) with an adequate volume resuscitation measures) at admission or during patient stay in ED; SOFA score at admission; Emergency surgery score; ACS NSQIP® Surgical Risk score.
- Radiological findings: CT-scan reports of patients selected will be analyzed by site data-collection centers with the aim to identify typical and atypical radiological findings (subdiaphragmatic free gas, free peritoneal fluid, bowel wall discontinuity, extraluminal oral contrast, extraluminal abscess, abdominal collections, fat stranding, portal venous gas, wall bowel thickening, pneumatosis and mucosal hyperenhancement).
- Surgery: Time of skin incision; Type and duration of surgery; source control surgery, Open Abdomen; surgical approach; site and cause of perforation; pathologic data; Emergency surgery score; ACS NSQIP® Surgical Risk score.
- Postoperative Course: Preoperative mortality (patients die before surgery); Medical and Surgical complications (Clavien-Dindo score); total LOS; LOS in ICU; days of Mechanical Ventilation; Re-intervention rate; 90-d mortality.
PLANNED SAMPLE SIZE With a binary response variable, β=0·95, α=0·05, an anticipated small effect size and an allocation ratio 1:10 (Early treatment Yes vs. No), it has been calculated that 3276 patients are required to detect an association between the variables and the endpoint.
PLANNED ANALYSES Time between patient admission to ED and surgery will be analyzed as a continuous variable with t-Student's tests, comparing means between the different outcomes (primary and secondary). Different cut-off will be tested to define a significant time threshold correlating with outcomes. If necessary, more time intervals will be evaluated to evaluate correlations between the variables collected and the time.
- Conditions
- Emergency Surgery
- Being tested
- Surgical timing from ED admission to surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical timing from ED admission to surgeryBehavioural
the impact of delay of time between patient admission to ED and surgery for source control on 90-d mortality and postoperative outcomes in patients with gastrointestinal perforation with or without septic shock
What is being measured
The primary outcome is the main question the study is designed to answer.
in-hospital Clavien-Dindo > 3 complication rate
Measured: up to 90 days after surgery
Secondary outcomes (6)
90-d mortality rate
Measured: up to 90 days after surgery
total length of stay (LOS)
Measured: up to 90 days after surgery
LOS in Intensive Care Unit (ICU)
Measured: up to 90 days after surgery
days of mechanical ventilation
Measured: up to 90 days after surgery
re-intervention rate
Measured: up to 90 days after surgery
30-d readmission rate
Measured: up to 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2021
- Study start1 Jan 2009
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Emergency SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 3,276 participants (estimated)
Sponsor and investigators
- Lead sponsor
- San Luigi Gonzaga Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rossella Reddavid, San Luigi Gonzaga Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04811755
- Sponsor's protocol ID
- TT.01
- Acronym
- TIME
- Status last verified
- Mar 2021
- First submitted
- 19 Mar 2021
- Last updated
- 23 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Azuhata T, Kinoshita K, Kawano D, Komatsu T, Sakurai A, Chiba Y, Tanjho K. Time from admission to initiation of surgery for source control is a critical determinant of survival in patients with gastrointestinal perforation with associated septic shock. Crit Care. 2014 May 2;18(3):R87. doi: 10.1186/cc13854.
PubMed 24886954Buck DL, Vester-Andersen M, Moller MH; Danish Clinical Register of Emergency Surgery. Surgical delay is a critical determinant of survival in perforated peptic ulcer. Br J Surg. 2013 Jul;100(8):1045-9. doi: 10.1002/bjs.9175.
PubMed 23754645Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
PubMed 28101605Sartelli M, Viale P, Catena F, Ansaloni L, Moore E, Malangoni M, Moore FA, Velmahos G, Coimbra R, Ivatury R, Peitzman A, Koike K, Leppaniemi A, Biffl W, Burlew CC, Balogh ZJ, Boffard K, Bendinelli C, Gupta S, Kluger Y, Agresta F, Di Saverio S, Wani I, Escalona A, Ordonez C, Fraga GP, Junior GA, Bala M, Cui Y, Marwah S, Sakakushev B, Kong V, Naidoo N, Ahmed A, Abbas A, Guercioni G, Vettoretto N, Diaz-Nieto R, Gerych I, Trana C, Faro MP, Yuan KC, Kok KY, Mefire AC, Lee JG, Hong SK, Ghnnam W, Siribumrungwong B, Sato N, Murata K, Irahara T, Coccolini F, Segovia Lohse HA, Verni A, Shoko T. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013 Jan 8;8(1):3. doi: 10.1186/1749-7922-8-3.
PubMed 23294512
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is TIme From adMission to surgEry an Independent Prognostic Factor for Survival of Patients With Gastro-intestinal Perforation Associated With Septic Shock: (TIME) An Italian Intersocietary Retrospective and Prospective Observational Trial
- ClinicalTrials.gov ID
- NCT04811755
- Acronym / sponsor ID
- TIME / TT.01
- Conditions
- Emergency Surgery
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 3,276 participants (estimated)
- Lead sponsor
- San Luigi Gonzaga HospitalUniversity, hospital or other
- Study start
- 1 Jan 2009 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 23 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Gastro-intestinal perforation is a condition that can become life-threatening in case of appearance of systemic symptoms, sepsis-related peripheral hypoperfusion and single or multiple organ failure needing a prompt intervention in Emergency Department (ED) setting. Literature reports disagreeing data about the effect of surgical timing on mortality and postoperative outcomes: Buck et al. described a 2.4 % of decreased survival every hour of surgical delay in case of perforated peptic ulcers. Other authors documented significantly longer postoperative hospital stay, greater health costs and a significant increase of postoperative complication and mortality rates when surgery is delayed in high-risk patients with comorbidities or age > 65 years. Azuhata described a highly significant relationship between delayed surgery and patients' survival: after 6 hours from admission to ED, patients with gastrointestinal perforation and associated septic shock don't survive to surgery. The aim of this study is to assess the impact of delay of time between patient admission to ED and surgery for source control on 30-d mortality and postoperative outcomes in patients with gastrointestinal perforation with or without septic shock. Furthermore, we want to define the time threshold within which surgery can affect patients' survival.
Detailed description
This is an Italian National multicenter study composed by a retrospective phase of data collection from patients of past ten years and a perspective one of next two years.
INCLUSION AND EXCLUSION CRITERIA We include in our analysis all patients with more than 18 years old undergoing emergency surgery for gastro-intestinal perforations, with or without signs of septic shock. All patients with covered perforations or abdominal perivisceral free air bubbles treated with non- operative management or delayed surgery will be excluded. An online Case Report Form (CRF) will be filled out by every participating Italian participating center.
ENDPOINTS Primary outcome analyzed is in-hospital Clavien-Dindo > 3 complication rate [12]. Secondary outcomes are 60-d mortality rate, total length of stay (LOS), LOS in Intensive Care Unit (ICU), days of mechanical ventilation, re-intervention rate and 30-d readmission rate.
Analyzed variables are:
- Hospital characteristics; teaching/non-teaching setting; I/II level ED; emergency surgery/volume x year; 24H/on-call radiology and surgery team; presence of a dedicated OR in ED;
- Patient demographics (gender, age, Body Mass Index (BMI) and American Society of Anaesthesiologists' (ASA) classification of Physical Health, medical history of past abdominal surgical operations and comorbidities according to Charlson Comorbidity Index (CCI), mainly related to corticosteroids therapy and immunosuppressive conditions),
- Patient management in ED: admission date and time; Priority code at admission; time of abdominal x-Ray; time of CT-scan; Time of patient evaluation by surgeon on- call; Preoperative resuscitation management (Y/N, type, time of beginning); presence of Sepsis (infection documented or suspected + SOFA >=2) and of septic shock (sepsis + persistent hypotension needing vasopressors to maintain a Mean Arterial Pressure (MAP) of 65 mmHg; serum values of lactates > 18 mg/dL (or 2 mmol/L) with an adequate volume resuscitation measures) at admission or during patient stay in ED; SOFA score at admission; Emergency surgery score; ACS NSQIP® Surgical Risk score.
- Radiological findings: CT-scan reports of patients selected will be analyzed by site data-collection centers with the aim to identify typical and atypical radiological findings (subdiaphragmatic free gas, free peritoneal fluid, bowel wall discontinuity, extraluminal oral contrast, extraluminal abscess, abdominal collections, fat stranding, portal venous gas, wall bowel thickening, pneumatosis and mucosal hyperenhancement).
- Surgery: Time of skin incision; Type and duration of surgery; source control surgery, Open Abdomen; surgical approach; site and cause of perforation; pathologic data; Emergency surgery score; ACS NSQIP® Surgical Risk score.
- Postoperative Course: Preoperative mortality (patients die before surgery); Medical and Surgical complications (Clavien-Dindo score); total LOS; LOS in ICU; days of Mechanical Ventilation; Re-intervention rate; 90-d mortality.
PLANNED SAMPLE SIZE With a binary response variable, β=0·95, α=0·05, an anticipated small effect size and an allocation ratio 1:10 (Early treatment Yes vs. No), it has been calculated that 3276 patients are required to detect an association between the variables and the endpoint.
PLANNED ANALYSES Time between patient admission to ED and surgery will be analyzed as a continuous variable with t-Student's tests, comparing means between the different outcomes (primary and secondary). Different cut-off will be tested to define a significant time threshold correlating with outcomes. If necessary, more time intervals will be evaluated to evaluate correlations between the variables collected and the time.
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients undergoing emergency surgery for gastro-intestinal perforations, with or without signs of septic shock
Key inclusion criteria (3 listed)
- more than 18 years old
- emergency surgery for gastro-intestinal perforations
- with or without signs of septic shock
Key exclusion criteria (2 listed)
- All patients with covered perforations or abdominal perivisceral free air bubbles treated with non- operative management
- delayed surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Surgical timing from ED admission to surgerythe impact of delay of time between patient admission to ED and surgery for source control on 90-d mortality and postoperative outcomes in patients with gastrointestinal perforation with or without septic shock | Behavioural | – |
Primary outcome
in-hospital Clavien-Dindo > 3 complication rate
Time frame: up to 90 days after surgery
6 secondary outcomes
90-d mortality rate
Time frame: up to 90 days after surgery
total length of stay (LOS)
Time frame: up to 90 days after surgery
LOS in Intensive Care Unit (ICU)
Time frame: up to 90 days after surgery
days of mechanical ventilation
Time frame: up to 90 days after surgery
re-intervention rate
Time frame: up to 90 days after surgery
30-d readmission rate
Time frame: up to 30 days after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2021.
- Results publication: PubMed 24886954Azuhata T, Kinoshita K, Kawano D, Komatsu T, Sakurai A, Chiba Y, Tanjho K. Time from admission to initiation of surgery for source control is a critical determinant of survival in patients with gastrointestinal perforation with associated septic shock. Crit Care. 2014 May 2;18(3):R87. doi: 10.1186/cc13854.
- Results publication: PubMed 23754645Buck DL, Vester-Andersen M, Moller MH; Danish Clinical Register of Emergency Surgery. Surgical delay is a critical determinant of survival in perforated peptic ulcer. Br J Surg. 2013 Jul;100(8):1045-9. doi: 10.1002/bjs.9175.
- Results publication: PubMed 28101605Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
- Results publication: PubMed 23294512Sartelli M, Viale P, Catena F, Ansaloni L, Moore E, Malangoni M, Moore FA, Velmahos G, Coimbra R, Ivatury R, Peitzman A, Koike K, Leppaniemi A, Biffl W, Burlew CC, Balogh ZJ, Boffard K, Bendinelli C, Gupta S, Kluger Y, Agresta F, Di Saverio S, Wani I, Escalona A, Ordonez C, Fraga GP, Junior GA, Bala M, Cui Y, Marwah S, Sakakushev B, Kong V, Naidoo N, Ahmed A, Abbas A, Guercioni G, Vettoretto N, Diaz-Nieto R, Gerych I, Trana C, Faro MP, Yuan KC, Kok KY, Mefire AC, Lee JG, Hong SK, Ghnnam W, Siribumrungwong B, Sato N, Murata K, Irahara T, Coccolini F, Segovia Lohse HA, Verni A, Shoko T. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013 Jan 8;8(1):3. doi: 10.1186/1749-7922-8-3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Emergency Surgery, run by San Luigi Gonzaga Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
in-hospital Clavien-Dindo > 3 complication rate (time frame: up to 90 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04811755, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2021.