Clinical trial NCT04480034: Obesity Surgery During 2020 Italian Pandemic
Official title: Laparoscopic Bariatric Surgery During Phase 2-3 Covid-19 Pandemic in Italy: a Multicenter, Prospective, Observational Study.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bariatric Surgery Candidate
Covid19
Complication of Surgical Procedure
Pneumonia, Viral
Viral Infection
Obesity, Morbid
Safety Issues
Readmission
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliero, Universitaria Pisana
name: Azienda Ospedaliera di Padova
name: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: IRCCS Policlinico S. Donato
name: University of Rome Tor Vergata
name: A.O.U. Città della Salute e della Scienza
name: Humanitas Clinical and Research Center
name: Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy
First posted: 2020-07-21
Enrollment: 1600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Since July 2020, all the bariatric cases performed in the 8 participating centers will be collected in a prospective database, to monitor the postoperative course of the patients until WHO will declare the end of the pandemic, in order to determine the incidence of Sars-Cov-2 infection after bariatric surgery.

All the data will be collected anonymously on a database by an independent data manager. The results will be evaluated in January 2021. As comparative group will be considered the patients operated during the period July/December 2019 in the same centers

Brief summary: The first person-to-person Coronavirus disease (COVID-19) transmission in Italy was reported on Feb 21st, 2020, causing one of the most massive outbreak in Europe so far that stopped immediately all elective surgical procedures. Bariatric surgery represents the most effective treatment to obtain an important, long-term weight loss and comorbidities' resolution, including respiratory disorders. A sensitive decrease of epidemic has been observed lately and a gradual and progressive stop of the lockdown (phase 2-3) was planned, when the virus is supposed to be under control and protocols are guiding the restart of the elective bariatric surgery. Several questions are currently open: Laparoscopic bariatric surgery is safe in the phase 2-3? What's the expected complications rate? The actual hospital protocols are effective to minimize the risk of postoperative COVID-19 infection? Aim: to analyse results of bariatric surgery during phase 2-3 COVID-19 pandemic in Italy. Primary end point: 30 days COVID-19 infection, mortality and complications. Secondary end points: readmission rate 30 days, reoperations for any reason related to surgery. Study design: prospective multicenter observational. Setting: Italian National Health Service 8 high-volume bariatric centres. Enrollment criteria: No previous Covid-19 infection; Primary, standard IFSO approved bariatric procedures; No concomitant procedure; No previous major abdominal surgery; \>18\<60 years old; Compensated comorbidities; Official SICOB's surgical informed consent given, including COVID-19 addendum; Adherence to very restrictive protocols regarding: hospital admission, management of in-hospital patients and after discharge. Follow-up: scheduled outpatient visit 30th postoperative day. Data evaluation: all the cases performed during July/December 2020 will be collected in a prospective database. Patients operated during the period July/December 2019 in the same centers will be considered comparative group (control). Expected results: Transparent information to the patients, and the introduction of the COVID-19 protocol concerning patients and health-professionals protection, should guarantee a safe restart of bariatric surgery in Italy. The network of 8 high-volume centers sharing information and protocols in this "unexplored" period will be a guarantee for patients' safety. Bariatric surgery should induce a postoperative amelioration of the comorbidities reducing the risks in case of a second outbreak.

Detailed description: Background Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . The disease was first identified in December 2019 in Wuhan, the capital of China's Hubei province, and has since spread globally, resulting in the ongoing 2019-20 coronavirus pandemic . As of 08.05.2020, more than 3.91 million cases have been reported across 185 countries and territories, resulting in more than 218,000 deaths. More than 1.344.000 people have recovered . Even though there are very few available data on BMI for patients with COVID-19 infections, the role of obesity in the COVID-19 epidemic must not be ignored. A recent study on patients admitted in China for pneumonia from SARS-CoV-2, showed that obesity is associated with higher risks to develop severe pneumonia, especially in men . Obesity plays an important role in the pathogenesis of COVID-19 infection . In fact, the immune system, which is a key player in the pathogenesis of COVID-19, also plays an important role in obesity-induced adipose tissue inflammation. This inflammation of adipose tissue results in metabolic dysfunction potentially leading to dyslipidaemia, insulin resistance, type 2 diabetes mellitus, hypertension, and cardiovascular disease. A systematic review and meta-analysis demonstrated that severe obesity (body mass index BMI ≥ 40 kg/m2) represents a major risk factor of intensive care unit admission or death in individuals affected by H1N1 influenza . Thereafter, obesity is associated with a higher risk of infectious diseases, in particular of the respiratory tract.

There are a number of factors predisposing subjects with obesity to viral infections. These factors include low-grade chronic inflammation with hyper-production of pro-inflammatory cytokines, reduced natural killer (NK) cell number and activity, altered CD4:CD8T cell balance, impaired response to antigen stimulation and high expression of adipocyte angiotensin type 1 and 2 receptors.

Furthermore, obesity is associated with, and responsible for, comorbidity conditions that may represent risk factors for serious COVID-19 infection (i.e. type II diabetes, ischemic cardiac disease, etc.). Extra attention and precautions for patients with obesity during this epidemic is recommended. Whenever COVID-19 infection is suspected, screening must be systematic, particularly if the patient has obesity.

So far, bariatric surgery represents the most effective treatment to obtain a long-term meaningful weight reduction and resolution of comorbidities including respiratory disorders. In a very large case series study including 56277 subjects who underwent bariatric surgery in the United States, the overall risk of developing common infectious diseases including respiratory infections decreased significantly in men during the first two years after surgery (aOR, 0.69 \[95% CI, 0.60-0.79\]; P\<0.001).

The first person-to-person transmission in Italy was reported on February 21st, 2020, in Lombardy region, the most crowded and rich region in Italy, causing the most massive Covid-19 outbreak in Europe so far. First positive cases of Sars-Co-v-2 were registered in Italy by 29th of January 2020. The COVID-19 outbreak stopped all elective surgical procedures by 9th of March, including bariatric/metabolic surgery except emergency conditions as suggested by recent IFSO recommendations . All elective surgical and endoscopic cases for metabolic and bariatric surgery should be postponed during the phase one outbreak. This would minimize risks to both patient and healthcare team, as well as reducing the utilization of unnecessary resources, such as beds, ventilators and personal protective equipment (PPE). In addition, postponing these services will minimize potential exposure of the COVID-19 virus to unsuspecting healthcare providers and patients.

To understand what could have been the impact of operating a population at risk of infection without specific precautions, we gathered a group of eight high-volume Italian bariatric centers, which performed 840 laparoscopic bariatric procedures during January and February 2020. Five are located in regions with high infection rates (Lombardy, Veneto, Piedmont, Emilia Romagna), and 3 are in areas with infection rate close to the Italian average (Tuscany, Lazio). A structured phone interview was administered to all patients operated during that period. We found five infections (5.9 cases out of 1000 inhabitants), four in Lombardy, and one in Veneto. The overall rate of infection on May 2, 2020, was similar in the 2 regions, 7.19 out of 1.000 inhabitants . Among infected patients, 2 had mild symptoms and home care, and three were hospitalized for fever and dyspnea; none died. Four out of five cases were over 60 years, all were female, and 3 out of 5 cases, reported an extra-hospital contact with positive COVID-19 people. All 5 cases healed eventually, with a negative swab.

During the last days of April 2020, a sensitive decrease of epidemic has been observed in Italy and Government planned a gradual and progressive stop of the lockdown (the so-called phase 2). That means the start of a new period when the virus is supposed to be under control and protocol are coming in the National Health Care System (SSN) to restart the elective surgical practice.

Several open questions are currently waiting the answers useful for the settlement of the management of obese patients, considering bariatric surgery effective for weight loss and co-morbidity control as well protective against eventual recurrent outbreak.

* Laparoscopic bariatric surgery is safe in the phase 2 outbreak?
* What's the expected complication rate of laparoscopic bariatric surgery in COVID-19 phase 2?
* The hospital protocols are effective to minimize the risk of postoperative Covid 19 infection after elective bariatric surgery in selected patients? Aim: to analyze results of laparoscopic bariatric surgery during phase 2 COVID-19 pandemic in Italy.

Primary end point: 30 days COVID-19 infection, mortality and complications. Secondary end points: readmission rate 30 days, reoperations for any reason related to bariatric surgery.

Study design: prospective multicenter observational Time interval: 12 months (July 2020 - May 2021): recruitment and therapy July 2020-December 2020, follow-up January 2021, data collection and analysis, manuscript preparation and publication Feb-May 2021).

Setting: Italian National Health Service' high-volume bariatric centres, academic hospitals.

Hospital admission protocol

1. Two to three days before admission, a doctor must interview the patient by telephone with the following questionnaire:

   * Did you have fever (threshold value \> 37.5ºC / 99.5ºF), especially in the last 48 hours?
   * Do you have any new respiratory symptoms, especially when you walk?
   * Do you have other symptoms: vomiting, diarrhea, conjunctivitis, changes in smell, or taste, osteoarticular pain, excessive fatigue?
   * Have you had contact in the last two weeks with a confirmed case (clinical diagnosis - positive swab) of COVID-19?
2. 24-48 hours before hospitalization, the patient must arrive at the hospital: outside the hospital, the medical staff must repeat the interview as above and must swab the patient. In the case of a positive swab, surgery must be suspended. In the case of negativity, the patient must receive and sign a specific COVID-19 consent, and the operation can be carried out, with hospitalization on the same day of the procedure.

These procedures are in line with international and national guidelines for the screening of patients before entry the hospital (12) Screening at admission

1. Standard interview (National accepted Covid-19 questionnaire, see attachment 1)
2. Fever check
3. Chest X-ray / Thoracic CT scan Surgical informed consent

1. SICOB approved informed consent for standard bariatric procedures (2014 version); 2. A modified informed consent including the risk of COVID-1919 infection, will be adopted and added by all centers to the standard, above listed official consent: "I am aware that this bariatric procedure may lead to an increase in the possibility of contracting the COVID-19 infection, due to the general situation currently present, with a possible further increase in postoperative complications. I am also aware that, following the intervention, I will have to undergo a 14-day postoperative quarantine period, I will have to measure the temperature twice a day, I will be prohibited from traveling and traveling. The first postoperative check-up will be performed at the end of this period, unless complications related to surgery arise." Operating Room (OR) protocol

* For surgeon standard personal protective equipment (PPE) plus N95 mask
* For anesthesiologists and nurses who manage the airways and gastric bougie positioning, we recommend using N99 mask, face shield, single-use waterproof gown, and double gloves
* At the end of each procedure, every PPE must be changed
* Restrict access to people in OR
* Expert surgeons and anesthesiologists must perform the procedures to minimize the OR occupation time.
* A smoke evacuator system should be employed to avoid aerosol contamination; in the alternative, a filter must be connected to the exsufflation system.
* A negative pressure in the OR is not mandatory, but it is crucial to allow enough time between cases for complete room air exchange. In case the OR had been used for intensive care during phase 1 pandemic, proper sanitization is required.

Management of in-hospital patients

* No Covid-19 hospital/section should be used for elective bariatric surgery.
* Standard PPE for staff is mandatory.
* Social distance must be respected even in case of post-surgical mobilization; patients should always wear a surgical mask.
* Each patient should have a single room, or in the case of a large room, he must be assigned a suitable space to comply with the laws in force on social distancing.
* ERAS protocol is welcomed whenever is possible.

After discharge:

* In case of intra-hospital contact with Covid-19 patient or healthcare professional, 14 days self-quarantine after discharge is mandatory
* Home physical activity (same proposed program for all groups)
* Implement Oral supplementation (proposed recommendation for all groups)
* Low dose heparin for at least three weeks (proposed treatment for all groups)
* After 7 and 15 days the patients receive a follow-up phone with specific questions about Covid-19 (attached structured phone interview) Follow-up: Scheduled outpatient visit: 30 postoperative day.

Eligibility criteria: Inclusion Criteria:

1. Primary bariatric surgery;
2. Compensated DMT2;
3. Controlled hypertension;
4. Patients with OSAS can only be admitted if therapy with home CPAP is effective
5. Laparoscopic standard bariatric procedure;
6. Procedure duration less than 120 minutes;
7. Official SICOB's surgical informed consent given, including Covid-19 addendum.

Exclusion Criteria:

* previous Covid-19 infection;
* patients who may need an extended stay or intensive care (BMI \> 60).
* concomitant procedure;
* previous major abdominal surgery

Primary outcomes:
measure: Postoperative COVID-19 infection
timeFrame: 30 postoperative days
Secondary outcomes:
measure: Complications related to bariatric surgery
timeFrame: 30 postoperative days
Other outcomes:
Locations:
city: Latina
country: Italy
facility: University La Sapienza of Rome, Department of Medico-Surgical Sciences and Biotechnologies
state: LT
Study officials:
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