Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05169164 |
| Other study ID # |
LASOS |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2022 |
| Est. completion date |
March 31, 2023 |
Study information
| Verified date |
August 2023 |
| Source |
University of Sao Paulo |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Methods: International, seven-day observational cohort study of complications following
elective or emergency surgery. Objectives: To provide detailed data describing post-operative
complications and associated mortality. Number of participants: Our aim is to recruit as many
patients from as many hospitals as possible in Latin American nations. Eligible countries for
participation: Countries and dependencies in Latin America that are situated in the area
stretching from the northern border of Mexico to the southern tip of South America, including
the Caribbean. Inclusion criteria: all adult patients aged 18 years or older undergoing
elective or emergency surgery during the seven-day study period with a planned overnight
stay. Exclusion criteria: patients who are undergoing planned day-case surgery or
radiological procedures. Statistical methodology and analysis: Single and multi-level
logistic regression models will be constructed to identify factors independently associated
with these outcomes and to adjust for differences in confounding factors. A single final
analysis is planned at the end of the study. A pre-defined analysis will focus on outcomes of
patients who have undergone caesarean section. Study duration: Each nation will select a
7-day period between 1st April and 31th October 2022.
Description:
Introduction
More than 310 million patients undergo surgery worldwide each year with reported hospital
mortality between 1 and 4%. Recent estimates suggest that 4.2 million deaths occur within 30
days of surgery, and half of these occur in low and middle-income countries (LMIC).
Complications are more common and are a leading cause of long-term morbidity and mortality.
The International Surgical Outcomes Study (ISOS) confirmed the association between
complications and death after surgery at a global scale, but predominantly included
high-income nations. More recently, the African Surgical Outcomes Study (ASOS) found that
patients undergoing surgery in African nations were twice as likely to die than those in
high-income countries (HIC), despite being younger with fewer co-morbid diseases. While there
is a global drive to improve access to surgery in LMICs there is a need to implement this
safely. Latin America describes a geographic area including 25 nations, and countries within
the region have some of the highest income disparity worldwide. Rapid demographic and
societal changes have led to an increasing burden of non-communicable disease. Provision of
healthcare varies widely within Latin America, with a mix of private, social and government
funded schemes. The investigators aim is to conduct a seven-day cohort study of adults
undergoing in-patient surgery in Latin America to provide detailed data describing
post-operative complications and associated mortality.
Study objectives
Primary objective To evaluate the incidence of 30-day in-hospital complications following
elective or emergency in-patient surgery
Secondary objective
- To describe the 30-day in-hospital mortality associated with these complications
- To describe the length of hospital stay
- To describe the pattern of postoperative critical care use
- To describe the effect of postoperative complications on duration of hospital stay
- To describe needs of critical care at postoperative
Primary outcome measure In-hospital post-operative complications of any cause, censored at 30
days following surgery for patients who remain in hospital
Secondary outcome measures
- In-hospital all-cause mortality censored at 30 days following surgery for patients who
remain in hospital
- Duration of hospital stay after surgery, censored at 30 days following surgery for
patients who remain in hospital
- Admission to critical care within 30 days of surgery during the index admission
Study design
LASOS is an international, observational seven-day cohort study. Data will be collected over
a four-month period, each national lead will select seven days over which participating sites
within their nation will collect data. The study will take place in Latin American countries
and dependencies defined as an area that stretches from the northern border of Mexico to the
southern tip of South America, including the Caribbean. All countries and dependencies listed
on the page 'Latin America' on Wikipedia as of 16th of September 2019 are eligible to take
part. All data collected will be that which is used for routine clinical care in hospital.
There will be no additional patient contact.
Study population
Each national group will select a single seven-day period for patient recruitment between 1st
April and 31st October 2022. Patients will be identified by the participating sites by review
of elective theatre lists, theatre logbooks, handover sheets, emergency admissions and ward
lists. All patients undergoing surgery over this period at a hospital taking part in the
study will be eligible for inclusion provided the participants meet the following criteria.
Inclusion criteria All adult patients (aged 18 years or older) undergoing elective or
emergency surgery with a planned overnight stay.
Surgery is defined as a procedure where a deliberate access to the body is gained via an
incision or percutaneous puncture, and where instrumentation is used in addition to the
puncture needle, or instrumentation via a natural orifice.
Exclusion criteria Patients who are undergoing planned day-case surgery or radiological
procedures.
Risks and benefits
Risks There are no safety considerations relating to the LASOS study. There is no risk of
harm to either patients or investigators. The risk of an information governance breach is
negligible because no patient identifiable data wil be collected outside each participating
hospital.
Benefits
1. to be the driver for improved perioperative care at a policy level in Latin American
countries
2. to provide a clear evidence base for further research in the region
3. to provide insights into surgical outcomes that may be applicable to other LMIC settings
Study procedures
Consent procedures Very similar studies have been successfully performed in more than 80
countries. The majority of nations participating in these in prior studies waived the need
for informed patient consent, given the dataset includes only those documented as part of
routine clinical care and that the data is collected in a fully anonymized format.
Given this precedence, the investigators anticipate that informed consent and ethical
approval will not be required for LASOS. The need for consent at each centre will be
determined by local coordinators, and a site agreement will be requested from each site lead
confirming that data is collected in accordance with local requirements.
Study data
Data will be collected on all eligible patients who undergo surgery during the study week for
that country. Centre specific data will be collected at the start of the study period.
Standard definitions for all outcomes will be provided to all centres. All relevant study
documents will be translated into Spanish, French and Portuguese, and data entry will be
available in those languages.
Data collection
Centre specific data will be collected once for each hospital including: university or
non-university hospital, number of hospital beds, number of operating rooms, number and level
of critical care beds, details about the reimbursement status of the hospital, university
hospital status, existence of residency programmes in anaesthesia, surgery, medicine or
critical care, availability of a rapid response team, if the hospital holds valid
accreditation (ONA, Qumentum or Joint Commission) and the ratio of nursing staff to hospital
beds in post-operative care areas.
Data will be collected in individual hospitals on a paper CRF for each patient recruited.
Paper CRFs will be stored within a locked office in each centre. This will include
identifiable patient data in order to allow follow-up of clinical outcomes. The CRF will be
completed for all participants, with separate data collection for patients having a caesarean
section.
Data will be anonymized by generating a unique numeric code ('LASOS ID') and transcribed by
local investigators onto an internet based electronic CRF. Patients will only be identified
on the electronic CRF by their LASOS ID. A patient list will be used in each centre to match
the LASOS ID to individual patients in order to record clinical outcomes and supply any
missing data points. Once the local coordinator confirms data entry is complete for their
hospital the coordinators will receive a spreadsheet of raw (un-cleaned) data, allowing
further checks for data completeness and accuracy.
Study group organization
LASOS will be led by the study management group who will be responsible for study
administration, communication between project partners, data collation and data management.
National coordinators will lead the project in each nation and:
- Identify local coordinators in participating hospitals
- Assist with translation of study paperwork as required
- Ensure distribution of study paperwork and other materials
- Ensure necessary regulatory approvals are in place prior to the start date
- Ensure good communication with the participating sites in his/her nation
Local coordinators in individual institutions will have the following responsibilities:
- Provide leadership for the study in their institution
- Ensure all relevant regulatory approvals are in place for their institution
- Ensure adequate training of all relevant staff prior to data collection
- Supervise daily data collection and assist with problem solving
- Act as guarantor for the integrity and quality of data collected
- Ensure timely completion of eCRFs by supervising local data entry
- Communicate with the relevant national coordinator
- Review and sign data sharing agreement at time of site opening.
End of study definition
The end of the study is defined as the end of the 30-day follow-up for the last patient
included. Data analysis will follow this.
Statistical considerations
Sample size All eligible patients during the recruitment period will be included. The
investigators do not have a specific sample size and statistical models will be adapted to
the event rate provided by the sample recruited.
Statistical analysis No comparison will be made between individual nations and all national
and institutional level data will be anonymized prior to publication. Categorical variables
will be described as proportions. Continuous variables will be described as mean and standard
deviation, if normally distributed, or median and inter-quartile range, if not normally
distributed.
Univariate analysis will be performed to test factors associated with post-operative
complications, admission to critical care and in-hospital death. Single-level and
hierarchical multi-level logistic regression models will be constructed to identify factors
independently associated with these outcomes and to adjust for differences in confounding
factors. Factors will be entered into the models based on biological plausibility and low
rate of missing data. Results of logistic regression will be reported as adjusted odds ratios
(OR) with 95% confidence intervals. The models will be assessed in sensitivity analyses to
explore possible interacting factors and examine any effect on the results. Imputation will
be considered for important missing variables. A single final analysis is planned at the end
of the study.
A pre-specified, separate analysis will be performed restricted to patients undergoing
caesarean section as this group have previously been identified as having very poor outcomes
compared to mothers in HIC.
Ethics
It is anticipated that requirements at participating nations will vary. This will vary by
nation and the study will be conducted in line with local legal and regulatory requirements.
In prior studies of this design across more than 80 countries, the vast majority of nations
have been happy to proceed without individual patient level consent. It is the national and
local investigators responsibility to clarify the need for ethics or other regulatory
approvals, and for ensuring these are in place prior to data collection. Centres will not be
permitted to record data without providing confirmation that the necessary ethics or other
regulatory approvals are in place.
The investigators will ensure that this study is conducted in accordance with the Principles
of the Declaration of Helsinki as amended in Tokyo (1975), Venice (1983), Hong Kong (1989),
South Africa (1996), Edinburgh (2000), Washington DC (2002), Tokyo (2004), Seoul (2008) and
Fortaleza (2013) as described at the following internet site:
https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-
research-involving-human-subjects.
Data handling and record keeping
Data management Data will be recorded on paper CRFs and uploaded onto the study database
where only anonymized data is collected. Each centre will also maintain an investigator site
file including a protocol, local investigator delegation log, CRFs, documentation of the
relevant regulatory approvals if applicable, screening log and patient list. The study
specific documents will be available to download on the LASOS study website. LASOS CRFs will
be stored securely in a locked cupboard and handled only by clinical staff familiar with
handling personal data.
Source data Since only routine clinical data is collected, the study CRFs will be completed
based on the hospital medical records, which are considered as source data for this study.
Confidentiality All identifiable data collected, processed and stored for the purposes of the
project will remain confidential at all times and comply with Data Protection Act, the
General Data Protection Regulation (GDPR), NHS Caldecott Principles, the UK Policy Framework
for Health and Social Care Research. Data will be collected by the patients' direct care team
and will be anonymized prior to transfer to the LASOS study management group. Access to the
data entry system will be protected by username and password, delivered during the
registration process for individual local investigators. All electronic data transfer between
participating centres and the coordinating centre will be encrypted using the SSL 3.0
protocol (HTTPS). Desktop and laptop security will be maintained through usernames and
passwords. The datacentre facilities are accredited to robust international standards that
are standard for transfer of healthcare data: ISO 27001, ISO 9001, ISO 14001 and PCI DSS. At
time of registration on the database entry portal, all users will review an information
governance document and electronically sign to confirm that the centre will abide by it.
Individual site data sharing agreements will be requested from the local coordinator.
Record retention and archiving All trial documentation and data will be stored for two years
after the main study findings are publicly reported, and then archived or destroyed by
participating hospitals according to local hospital policies. Electronic data sets will be
stored indefinitely.
Data management and ownership In line with the principles of data preservation and sharing,
the steering committee will, after publication of the overall dataset, consider all
reasonable requests to conduct secondary analyses. The primary consideration for such
decisions will be the quality and validity of any proposed analysis. Only summary data will
be presented publicly and all national, institutional and patient level data will be strictly
anonymized. Individual patient data provided by participating hospitals remain the property
of the respective institution. Once each local coordinator has confirmed the data provided
from their hospital are both complete and accurate, the centre will be provided with a
spreadsheet of the raw (un-cleaned) data for their hospital. The complete LASOS dataset,
anonymized with respect to participating patients, hospitals and nations, will be made freely
and publicly available two years following publication of the main scientific report. Prior
to this, the steering committee is not under any obligation to release data to any
collaborator or third party if the steering committee believe this is not in keeping with the
wider aims of the LASOS project.
Safety reporting
The trial involves negligible risks to patients and investigators, as it involves only
collection of anonymized routinely collected data. Adverse events will not be monitored or
reported.
