Condition category
Digestive System
Date applied
20/11/2006
Date assigned
21/12/2006
Last edited
11/04/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Fausto Catena

ORCID ID

Contact details

Via Lidice 4
Bologna
40139
Italy
fcatena@aosp.bo.it

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

FC111

Study information

Scientific title

Acronym

The ACTIVE (Acute Cholecystitis Trial Invasive Versus Endoscopic)

Study hypothesis

In the developmental stage of Laparoscopic Cholecystectomy (LC) it was considered 'unsafe' or 'technically difficult' to perform laparoscopic cholecystectomy for acute cholecystitis. However, with increasing experience in laparoscopic surgery, a number of centres have reported on the use of laparoscopic cholecystectomy for acute cholecystitis, suggesting that it is technically feasible but at the expense of a high conversion rate, which can be up to 35% and common bile duct lesions.

Several randomised studies in the early 1980s had shown that performing early open cholecystectomy (Laparotomic Cholecystectomy [LTC]) for acute cholecystitis was better than delayed cholecystectomy in terms of shorter hospital stay but both had similar operative morbidity and mortality rates. Early surgery had since gained in popularity in the late 1980s.

Routine use of the open procedure might enable more patients to have the operations during the acute phase because most surgeons are practiced in this approach. The impact of hospital stay and morbidity must also be taken into account. There is the expectation that open operation is associated with more pain and longer hospital stay.

In some trials successful laparoscopic cholecystectomy during the period of acute inflammation is associated with an earlier recovery and shorter hospital stay when compared with open cholecystectomy. Other studies did not confirm these results and the potential advantages of early laparoscopic cholecystectomy could be offset by a high conversion rate to open surgery. Moreover in these studies a similar postoperative programme to optimise recovery comparing laparoscopic and open approaches was not standardised. Many studies also do not report all eligible patients and are not double blinded.

Ethics approval

Approved by the ethical Committee of the S’Orsola-Malpighi Hospital, Bologna, Italy, on the 8th November 2005 (ref: 132/2005/U/Sper).

Study design

The study project is a prospective, multicentre randomised, double-blind, controlled trial.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Acute Cholecystitis

Intervention

AC is a common disease. Any improvement in this field will benefit many patients reducing morbidity, mortality, conversion rate, operation time, hospital stay, postoperative pain, return to normal activity and aesthetic result. All our patients will be informed about the study and an informed consent will be obtained. There will not be inconveniences caused to the patients. All the medical information obtained from the patients will be kept confidentially among the research scientists conducting the study. The patients will be free to withdraw from the study, whenever they want without any obligation.

The study will be performed in the Department of Emergency Surgery, St Orsola-Malpighi University Hospital (Bologna, Italy), a large teaching institution, and (together with other selected centres) with the participation of all surgeons who accept to be involved in the study.

On admission, the patients were started on cefotaxime, 2 g Intravenous (IV) every 12 hours, which was continued postoperatively according to National Nosocomial Infection Surveillance System (NNISS) score.

The patients will be divided in two groups:
1. Early LC within 72 hours after the diagnosis
2. Early LTC within 72 hours after the diagnosis

A surgeon that had performed at least 50 LCs will perform the procedure itself.

The standard four-trocar operative technique is used for LC for acute cholecystitis.
When the gallbladder is distended it will be first aspirated. To allow a good hold on the gallbladder larger graspers will be inserted through a 5 mm right lower port. The cystic artery and duct are clip-ligated. The gallbladder and intraperitoneal "dropped" stones are collected in an endoscopic bag and extracted through the umbilical cannula site, which can be extended. A closed system suction drain is left. Fascial closure is attempted only at the umbilical cannula site. The skin at all the cannula sites will be closed with staples.

The Laparotomic (LTC) procedure is carried out with an 8 cm right subcostal incision and the traditional surgical technique with a closed system suction drain left in situ.

Data Collection:
Patients' data sheets are generated containing demographic data and preoperative, operative, and postoperative information.

Pre-operative notes concern the history of gallbladder stones, the presence of associated diseases (cardiac, hypertension, diabetes, malignancy), duration of gallbladder complaints (as an indication for the onset of the disease), finding of a palpable gallbladder, temperature, and laboratory results of WBC count, serum bilirubin, gamma-glutamyl transferase (GGT), Polymerase Chain Reaction (PCR), Interleukin-6 (IL-6) and alkaline phosphatase. Ultrasound findings are also reported.

Operative data of concern are macroscopic findings (of acute cholecystitis, gangrenous cholecystitis, hydrops, and empyema of the gallbladder), the presence of small stones (less than 1 cm diameter) or large bile stones (more than 1 cm diameter), information regarding perforation of the gallbladder and intraperitoneally "lost" stones, reasons for conversion, and duration of surgery.

Postoperative notes of interest included the use of nasogastric tubes and drains, the amount of analgesics used, (evaluation of pain with Visual Analogue Scale [VAS] score), complications, and length of hospital stay.

Complications are classified as:
1. Surgical infections (wound infection, subphrenic or subhepatic abscess)
2. Non-infectious surgical problems (e.g., bile duct injury, haemorrhage)
3. Remote infections (urinary or respiratory)
4. Miscellaneous problems (e.g., atelectasis, deep vein thrombosis, Acute Myocardial Infarction [AMI], Cerebro-Vascular Accident [CVA], etc).

The collected information is entered into a database as either continuous or categorical variables for statistical analysis. Following the operative procedure, a large sterile dressing will be applied to cover the entire abdomen.

A second surgical team, aware of the operative findings but not the surgical access approach, will then assume the care of the patient. The second surgical team will determine postoperative care and ability to be discharged from the hospital. This second surgical team will be blinded to the surgical approach. The primary operative team will be in every moment available for emergent consultation or evaluation of the wound.

In the pre-anaesthetic holding area, baseline pain will be investigated at rest and on coughing using a pain-rating scale system: a 100 mm Visual Analogue Scale (VAS) (0 = minimal and 100 = maximal).

An investigator blinded to the study operation performed will evaluate postoperative pain intensity on returning to the Surgical Ward (zero time), and after 12 and 24 hours (± three hours). The three hours of tolerance (before or after the precise time of control) will be used in order to avoid waking the patients during the night. But during the day, if asleep, the patient will be awakened for the pain test.

At these timed intervals, the following variable will be recorded: VAS for pain at rest, and on coughing. If, at rest, VAS is more than three, the patient will be given intravenous 30 mg ketorolac. The pain tests will be also performed whenever the patient asks for additional analgesia between the timed controls, and parenteral analgesics will be administered accordingly. Every time the patient undergoes the pain test, he will be asked about the location of pain (in the surgical wound, far from the wound, everywhere or does not know). As soon as patients will begin to drink fluid instead of ketorolac 30 mg IV, they will be offered nimesulide 100 mg one tablet orally as often as necessary (maximum of two tablets daily). Orally administered analgesics will be continued in preference to parenterally administered analgesics if they will be efficacious.

After discharge, the patients will be offered nimesulide 100 mg one tablet orally as often as necessary (maximum of two tablets daily). Also parenteral and oral analgesic drug requirements will be recorded and analysed as a measure of postoperative pain. Furthermore the patient satisfaction with the analgesia provided (using a scale of poor, satisfactory, good, or excellent) will be recorded before discharge and after seven days.

Patient discharge will be based on good medical practice criteria:
1. Apyrexia
2. Absence of diseases requiring hospitalisation
3. Return of bowel function
4. Patient’s compliance

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

To evaluate the value of laparoscopic cholecystectomy to reduce hospital stay

Secondary outcome measures

1. To evaluate the value of laparoscopic cholecystectomy to reduce postoperative pain
2. To evaluate the conversion rate

Overall trial start date

01/01/2007

Overall trial end date

01/01/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adult patients (more than 18 years)
2. Clinical (pain, fever more than 37.5°C, White Blood Cells (WBC) more than 10,000/microL), and ultrasound evidence of cholecystitis
3. American Surgical Association (ASA) grade I to III patients
4. Informed consent
5. Less than 72 hours from onset

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

144

Participant exclusion criteria

1. Informed consent refusal
2. Choledocholithiasis
3. Generalised peritonitis
4. Previous abdominal surgical procedures
5. Patients with an intra-operative findings of different pathology will be excluded from the study
6. Apache II score more than ten

Recruitment start date

01/01/2007

Recruitment end date

01/01/2008

Locations

Countries of recruitment

Italy

Trial participating centre

Via Lidice 4
Bologna
40139
Italy

Sponsor information

Organisation

Italian Polispecialistic Society of Young Surgeons (Italy)

Sponsor details

Via Lidice 4
Bologna
40138
Italy
ctalarico69@hotmail.com

Sponsor type

Research organisation

Website

Funders

Funder type

Hospital/treatment centre

Funder name

St Orsola-Malpighi University Hospital (Italy)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24634923

Publication citations

  1. Results

    Catena F, Ansaloni L, Bianchi E, Di Saverio S, Coccolini F, Vallicelli C, Lazzareschi D, Sartelli M, Amaduzzi A, Amaduzz A, Pinna AD, The ACTIVE (Acute Cholecystitis Trial Invasive Versus Endoscopic) Study: multicenter randomized, double-blind, controlled trial of laparoscopic versus open surgery for acute cholecystitis., Hepatogastroenterology, 2013, 60, 127, 1552-1556.

Additional files

Editorial Notes