Clinical trial NCT01780285: Laparoscopic Repair of Giant Hiatal Hernias With Nitinol-framed Lightweight Polytetrafluoroethylene Mesh
Official title: Prospective Randomized Phase III Study of Laparoscopic Repair of Giant Hiatal Hernias With Nitinol-framed Lightweight Polytetrafluoroethylene Mesh
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hernia, Hiatal
Keywords: Hiatal hernia
Gastro-oesophageal reflux disease
Laparoscopic hiatal repair
Laparoscopic anti-reflux surgery
Partially absorbable lightweight mesh
Polytetrafluoroethylene
PTFE
Nitinol
Nitinol-framed lightweight PTFE mesh
Lead sponsor: Odessa National Medical University
Sponsor class: OTHER
First posted: 2013-01-31
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is prospective randomized trial enrolling at least 50 participants which compares efficacy and safety of two alternative methods of laparoscopic hiatal repair for giant (i.e. with hiatal surface area (HSA) exceeding 20 sq.cm) types II and III hiatal hernias: partially absorbable lightweight mesh repair, and nitinol-framed lightweight polytetrafluoroethylene (PTFE) mesh repair. In the literature, mean rate of anatomical recurrence of giant hiatal hernias is 25 %, reaching 42 %. Polypropylene and composite PTFE meshes used most widely, result in unacceptable rates of long-term dysphagia (10-15 %) and oesophageal strictures. Own experience of the interventors of more than 400 repairs using partially absorbable lightweight mesh Ultrapro (Ethicon) and original sub-lay technique of its fixation precluding contact of the mesh with the oesophagus, showed low recurrence rate for large hernias and a few cases of long-term dysphagia. For giant hiatal hernias, this technique provides acceptable results (20 % of recurrence) which correspond to the literature. Nevertheless, these results may be improved, probably by using of new type of prosthesis. Thus, in collaboration with Minnesota Medical Development, Inc., USA, the interventors created fundamentally new method of hiatal repair by using new prosthesis - Rebound HRD-Hiatus hernia. This prosthesis is heart-shaped lightweight PTFE mesh with peripheral nitinol frame. It is easily fixated to the crura posteriorly to the oesophagus completely covering hernia defect, and supports a strong framework of the hiatus, and, therefore, allows to save a principle a real tension-free repair. Mid-term results (mean follow-up period of 15 months) of 29 procedures showed no recurrences or oesophageal complications. Naturally, final conclusions regarding superiority of the new technique could be established by prospective randomized study. The hypothesis of the current trial is: new method of nitinol-framed lightweight PTFE mesh repair is more effective in terms of recurrence rate compared to sub-lay partially absorbable lightweight mesh repair, and is characterized by at least similar safety in terms of oesophageal complications. The long-term results (24 months post surgery for every patient) will be studied using symptom questionnaires, quality of life and satisfaction questionnaires, barium studies, endoscopic examinations, 24-hour pH testing, and analysis of possible reoperations.

Detailed description: Giant hiatal hernias, i.e. hernias with hiatal surface area (HSA), as described by Granderath et al (2007), exceeding 20 sq.cm, is one of the most challenging problem in minimally invasive gastrointestinal surgery. On one hand, according to the literature, the rate of utilization of laparoscopic repair of such hernias does not exceed 80 % \[Nguyen et al, 2011\]. It means that great proportion of patients is still treated using open approach producing 8 % of postoperative complications \[Nguyen et al, 2011\]. Therefore, improvement of laparoscopic techniques for this disorder is very actual question. On the other hand, the mean rate of anatomical recurrence following laparoscopic repair of paraoesophageal hernias is 25 % as reported in a meta-analysis \[Rathore et al, 2007\]. It reaches 42 % in some centers according to recent literature reviews \[Draaisma et al, 2005; Johnson et al, 2006\]. Hence, creation of new method of hiatal repair diminishing recurrence rate is essential. To interventors' opinion, this new method must follow at least a principle of tension-free repair.

As the most concerning problem or repair of giant hiatal hernias is anatomical recurrence, a conception of prosthetic repair was applied for hiatal closure using different types of meshes. This dramatically decreased recurrence rate as demonstrated by several recent studies. Namely, Frantzides et al (2002) prospectively compared primary repair with on-lay PTFE repair and obtained statistically significant decrease of recurrence rate in favor of mesh arm: 0% versus 22%. Then, Granderath et al (2004) compared primary suturing and on-lay polypropylene mesh repair in prospective randomized trial; the rate of recurrence was significantly lower in the mesh arm: 8% versus 26%. Unfortunately, these studies were not primarily addressed to relation between hernia size and results. Most specialists use mesh when the diameter of the defect is just greater than 5 cm, based on own experience and widespread literature data, including studies of Champion et al (1998, 2003). Hiatal surface area (HSA), first described by Granderath et al (2007), is more sensitive measure than diameter of hiatal hernia defect, and further trials should focus on it.

However, SAGES trial reported by Frantzides et al. (2010) showed that polypropylene or PTFE meshes are characterized by the highest incidence of oesophageal complications although they demonstrated relatively lower recurrence rates compared to other meshes. According to most of the literature, mesh-related dysphagia rate is 10-15 % in the long-term follow-up \[Granderath et al, 2005, Targarona et al, 2004\]. Interestingly, that composite, i.e. partially absorbable meshes, occupied middle position in terms of recurrence and complications rates in this study \[Frantzides et al, 2010\]. Own experience of the interventors of more than 400 laparoscopic hiatal repairs using lightweight partially absorbable mesh (Ultrapro, Ethicon) showed minimal rate of recurrence (4,9 %) and dysphagia (2,1 %) for large (HSA 10-20 sq.cm) hernias \[Grubnik et al, 2011\]. The interventors applied this safe technique for giant (HSA \> 20 sq.cm) hiatal hernias, but recurrence rate was 20 % \[Grubnik et al, 2011\]. This result corresponds to the literature, but may be improved. The interventors believe, it is possible to minimize recurrence rate of giant hiatal hernias, but it could be achieved by introduction of fundamentally new types of prostheses and methods of its fixation.

To remove the risk of mesh-related oesophageal complications of polypropylene or PTFE meshes, biological prostheses were introduced for hiatal repair. However, prospective randomized study by Oelschlager et al (2010) demonstrated insignificant difference in recurrence rates in prosthesis arm compared to primary repair arm (more than 50 %), although no cases of mesh-related complications were observed in prosthesis arm. Similar data regarding biological prostheses were retrieved in the study of Frantzides et al (2010). Data from the literature and international congresses suggest that current biological prostheses cannot be widely used in the setting of giant hiatal hernias due to high rate of recurrences and their high price. Thus, based on current literature data, there is insufficient grade 1 evidence for choice of optimal method of repair of giant hiatal hernias, and the search for the optimal prosthesis is still ongoing.

Therefore, a fundamentally new prosthesis for laparoscopic repair of giant hiatal defects was created. The prototype prosthesis "Rebound HRD-Hiatus hernia" was created by the interventors in collaboration with U.S. company, Minnesota Medical Development, Inc. This device is made from high quality lightweight PTFE mesh attached to a heart-shaped nitinol frame with a notch for oesophagus. Prosthesis may be easily inserted through the trocar using a special tube, and expanded to its initial form inside the abdomen. The principle and purpose of using of the device and method of its fixation was patented in Ukraine (patents No. 66397, 66399). The interventors applied new prosthesis in 29 patients, operated from 2010. All procedures were successfully completed. Two main principles are used in a new prosthesis. First, mesh is made of lightweight PTFE minimizing possibility of adhesions and related complications. As a result, there were no esophageal complications in the cohort. Second, peripheral nitinol frame of the prosthesis provides real tension-free repair without risk of prolapse between free, i.e. anterior, margin of the mesh and oesophagus, which other meshes do if fixed to the borders of the hiatus. As a result, there were no recurrences within mean surveillance of 15 months in this series. Naturally, final conclusions regarding superior efficacy and safety of the new device could be established by prospective randomized study.

Therefore, the hypothesis of this double-blind prospective randomized trial is: new method of nitinol-framed lightweight PTFE mesh (Rebound HRD-Hiatus hernia, Minnesota Medical Development, Inc) repair is more effective in terms of recurrence rate compared to sub-lay partially absorbable lightweight mesh (Ultrapro, Ethicon, Inc) repair, and is characterized by at least similar safety in terms of oesophageal complications.

The study will enroll at least 50 patients with giant (HSA \> 20 sq.cm) types II and III hiatal hernias. The basic eligibility criteria will be: absence of oesophageal motility disorders, absence of oesophageal shortening requiring Collis procedure, absence of Barrett's oesophagus, peptic strictures and other factors that may independently influence the rate of recurrence and dysphagia/oesophageal strictures. Thus, the only difference between arms will be method of hiatal closure. To exclude fundoplication-related bias, standard floppy-Nissen procedure will be performed in every patient.

Every patient will be operated by single surgical team with an experience of more than 1500 laparoscopic anti-reflux procedures since 1998. The necessary ethic regulations will be saved including informed consent with the statement that patient is unaware of the method of repair (double-masked). Every patient will be evaluated preoperatively, 6 months, and 24 months postoperatively using symptom questionnaires, quality of life and satisfaction questionnaires, barium studies, endoscopic examinations, 24-hour pH testing, and analysis of possible reoperations. For issue of efficacy of prosthetic repair, recurrence rate of hernia and GERD, which are the primary outcome measure, will be studied. For issue of safety of prosthetic repair, rates of long-term dysphagia/oesophageal strictures/mesh erosions, which are main secondary outcome measure, will be evaluated.

Eligibility criteria: Inclusion Criteria:

* Type II and III hiatal hernias, including complicated by GERD,
* Able to undergo elective laparoscopic hiatal hernia repair,
* Able to 24 months follow-up with office examinations,
* Hiatal surface area (HSA) exceeding 20 sq.cm (by Granderath et al, 2007) which correspond to the diameter of hernia defect exceeding 8 cm (the distinct size is determined intraoperatively, those with smaller diameter will be excluded from the study),
* Nissen fundoplication (intraoperative criterion)

Exclusion Criteria:

* Unable to undergo laparoscopic hiatal hernia repair due to: severe comorbidities (ASA III and more), previous major surgery with severe adhesions, etc.
* Cases of conversion to open surgery
* Age \< 20 years and \> 80 years
* BMI \< 16 and \> 39 kg/sq.m
* Pregnancy or plans for pregnancy within next 2 years (in females)
* Uncorrectable coagulopathy and immunosuppression
* Oesophageal motility disorders
* Oesophageal peptic strictures
* Oesophageal diverticula, other types (i.e. non-reflux) of chronic esophagitis, connective tissue disorders (e.g. scleroderma)
* Oesophageal shortening (determined intraoperatively as inability to achieve intra-abdominal length of oesophagus at least 3 cm in spite of intramediastinal oesophageal mobilization)
* Barrett's oesophagus
* History of oesophageal/gastric/duodenal surgery including vagotomy
* Relapsing course of ulcer disease/hyperacid gastritis including complicated by delayed gastric/duodenal emptying

Primary outcomes:
measure: Anatomical and functional recurrence of hiatal hernia and GERD
timeFrame: 24 months
Secondary outcomes:
measure: Repair-related dysphagia/oesophageal stricture/prosthetic erosion
timeFrame: 24 months
measure: Quality of life and satisfaction
timeFrame: 24 months
measure: Morbidity
timeFrame: 1 month
measure: Time to discharge
timeFrame: 1 month
measure: Number of participants completely recovered from extra-oesophageal complications of hiatal hernia following surgical procedure
timeFrame: 24 months
Other outcomes:
Locations:
city: Odessa
country: Ukraine
facility: Department of surgery No. 1 of Odessa national medical university, Odessa regional hospital
state: Ukaraine
Study officials:
affiliation: Department of surgery No. 1 of Odessa national medical university
name: Volodymyr V. Grubnik, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References:
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