Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03856710 |
| Other study ID # |
0874/2017/CTN |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 22, 2017 |
| Est. completion date |
May 31, 2025 |
Study information
| Verified date |
January 2024 |
| Source |
Doncaster And Bassetlaw Hospitals NHS Foundation Trust |
| Contact |
Srinivasan Balchandra, MS, MD, FRCS |
| Phone |
00447500856747 |
| Email |
srinivasan.balchandra[@]nhs.net |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Inguinal (groin) hernias are common and occur when an internal part of the body pushes
through a weakness in the surrounding tissue wall of the groin. They are more likely to occur
in men and affect people's quality of life by causing pain that is worse after any strenuous
activity. If untreated they can cause serious problems such as strangulation when too much
bowel comes through the weakness and becomes squeezed with the risk of losing blood supply
requiring emergency surgery. To prevent such complications, elective surgery for symptomatic
inguinal hernias is undertaken either in the conventional open method which involves a cut in
the groin, or the keyhole surgery, when the surgery is undertaken via three small incisions
in the abdomen (instead of a single, larger groin incision), a thin tube containing a light
source and a camera (laparoscope) is inserted through one of these incisions, so the surgeon
can see inside the abdomen. Special surgical instruments are inserted through the other
incisions, so the surgeon can pull or push the hernia back into place and a piece of mesh is
then stapled or glued to secure it to the weakened area in the abdomen wall. Securing the
mesh with staple has been associated with increased post-operative pain and analgesia
requirement; whereas not doing so has been thought to increase the chances of recurrence-
more so in large sized weakness. A newer mesh appears to offer benefit over conventional
meshes as it grips the tissues around the weakness without requiring staples or glue to fix
it in place, and has shown to cause lesser post-operative pain and recurrence.
This study is going to compare the newer self-gripping mesh with the conventional mesh
requiring fixation to see which is best for patients undergoing keyhole repair to fix
inguinal hernias.
Description:
Design: Double Blinded Randomised Controlled Trial This is a multicentre randomised
controlled trial in the setting of two district general teaching hospitals serving an
aggregate population of over 750 000. There are already established general surgical clinics
and operating sessions available for and including study patients. Both units undertake
conventional open and laparoscopic treatments for inguinal hernias on a regular basis in
keeping with the national average numbers.
Methodology; Patients with symptomatic unilateral or bilateral inguinal hernias diagnosed
clinically &/or radiologically will be identified at general surgical clinics and the primary
investigator, will arrange the following;
- Assess inclusion / exclusion criteria for participation in study
- Informed written consent for participation in the study
- Baseline clinical severity and quality of life analysis using:
- Euroqol (EQ5D)
- Core Outcome Measures Index adapted for patients with hernia (COMI-hernia)
- Informed written consent for intervention (the patient will be blinded as to the
intervention group) Subjects; Patients will be identified during attendance to our
general surgical clinics. Patients will be clearly informed that participation in the
study is entirely voluntary and that refusal to participate will in no way disadvantage
them.
Intervention (within 3 months of randomization);
- Re-assess inclusion / exclusion criteria
- Ensure informed written consent for surgery / participation in the study
- Intervention; The initial laparoscopic approach will be the same for both groups until
the process of selection and placement of the mesh (ProGripTM self-gripping mesh versus
standard 'lightweight' (large pore) polypropylene mesh fixed with SecurestrapTM) which
would be decided by randomization by sealed envelope into one of the 2 intervention
groups: Group 1 (Self-gripping Mesh), Group 2 (Stapled Mesh). The surgeon will have a
choice of Transabdominal Preperitoneal (TAPP) or Total Extraperitoneal (TEP) to perform
the laparoscopic inguinal hernia repair. Both TAPP and TEP are standard laparoscopic
techniques used for treatment of inguinal hernias both within the National Health
Service (NHS) and across the world.
Postoperative Care Since most laparoscopic inguinal hernia repairs are performed as day
cases, patients may be discharged on the same day of surgery after recovery with simple
analgesia. Diet can be resumed immediately and the convalescent period is expected to be 1-2
days with routine activities expected to resume at 2 weeks.
Blinding precautions:
Patients will be unaware of the type of mesh received as the randomisation process will be
carried out intraoperatively when the patient is under general anaesthesia. Subsequently,
over the follow-up period every possible effort will be made to continue the blinding process
in order to minimise any bias in patient reported outcomes.
Perioperative outcome measures
- Time taken for procedure
- Admission / 30-day readmission rates
- Procedure-specific complications
- Direct (marginal) costs Post-operative assessments Performed at 1 week, 6 weeks, 3
months and 12 months (by Surgical Registrar blinded to the intervention received by the
patient). 1 Week and 3 month follow-up will be over telephone (with a view to review
patient in the Hospital, should any concerns be expressed or elicited from the patient);
6 weeks and 12 month follow-up will be face-to-face in an out-patient clinic setting.
At each assessment the following will be analysed:
1. Pain - recorded prospectively in a diary by the patient independently. Recorded daily
for the first week on an un-marked 100mm long scale, from absolutely no pain to the
worst imaginable pain
2. Analgesia requirements - recorded daily for the first week in a diary by the patient
independently
3. Extent of ecchymosis, seroma/haematoma - The registrar will assess for any signs of
ecchymosis, seroma or haematoma and measure the magnitude of surface area(s) affected at
6 weeks.
4. Time to return to work and normal activities - reported by the patient. (Post-op all
patients will be advised to mobilise and return to normal activities as soon as they
feel able)
5. Procedure-specific complications;
6. Clinical efficacy and effectiveness; using
- Euroqol (EQ5D)
- Core Outcome Measures Index adapted for patients with hernia (COMI-hernia)
- Patient satisfaction rating scales
7. Cost effectiveness and cost benefit; using
- Direct costs
- Indirect costs
- Willingness to pay data
Quality of life and economic analysis;
- Generic Euroqol (EQ5D) instrument
- Core Outcome Measures Index adapted for patients with hernia (COMI-hernia) The
combination of these generic EQ5D and disease specific COMI-hernia tools are thus
sensitive to assess & compare both multidimensional and cost-effectiveness outcomes in
patients undergoing surgical treatment for inguinal hernia repair.
- Procedure-specific complications
- Patient satisfaction rating scale
- Cost effectiveness analysis; will be analysed in terms of
- Cost / symptom-free patient
- Cost / QALY (Quality-Adjusted Life Years) calculated from the EQ5D and COMI-hernia
indices Direct hospital costs will be collected prospectively with the help of the
hospital finance department; whilst indirect patient cost data (income loss,
domestic support etc.) will be assessed and calculated at interview at 3 and 12
months. Direct & indirect costs will provide total costs for use in the cost/QALY
calculations.
- Cost benefit analysis; outcomes, expressed as monetary units assessed by direct
willingness to pay (WTP) questioning, at 3 and 12 months will be used for cost benefit
analysis e.g. cost / £ willing to pay and cost / percent of weekly income willing to
pay.
Data collection and analysis Data will be collected and entered onto a specifically designed
Microsoft Access database Data distribution will be studied and analysed appropriately.
Intergroup analysis will be performed using Mann-Whitney U test and intragroup analysis will
be performed using the Friedman test across time points and Wilcoxon's ranked sum test
between two time points. Regression techniques and multivariate analysis will then be
utilised for a more thorough interrogation of the data.
For the economic analysis, the incremental cost per QALY of the intervention will be
assessed. This follows the example of National Institute of Clinical Excellence (NICE) who
use a threshold of £20 000 to £30 000 per QALY gained. However, cost-effectiveness analysis
is conducted under conditions of uncertainty. Cost effectiveness acceptability curves (CEACs)
will be generated to demonstrate the uncertainty around the decision. Given the data
available within the model, the CEAC will plot the probability of one strategy being more
cost-effective than the others for a range of threshold values of an additional QALY.
Interim Analysis:
An interim analysis will be carried out after recruitment of 25 patients per group. The goal
of this analysis is to evaluate recruitment rates, adverse events and serious adverse events
if any, as well as the overall viability and conduct of the trial.
The reported rates of moderate to severe chronic groin pain affecting QoL after elective
hernia repair ranges between 0 to 36%8-11. The variation is also attributed to the
inconsistencies in the definition of chronic pain. Investigators have taken the chronic pain
rates from one of the larger reported series (Garg et al 200937) to calculate the sample size
as their rates may be similar to the predicted chronic pain rates when fixing moderate to
large sized defects with permanent fixation devices. The sample size of 47 per group
(allowing for a dropout rate of 15%) will therefore be a pragmatic number to achieve
recruitment, follow-up and completion of the trial within the anticipated time period.
However the sample size derived from the meta-analysis (Sajid et al 201338) will be
considered for a future multi-centre trial that is planned by investigators' group based on
the outcomes from this pilot study.
Ethical issues;
- All patients will be given adequate time to read the patient information sheet
- No undue pressure will be exerted on any individual to participate in the study
- The patient consent form will be signed by the patient and the researcher, only when
both are happy that the patient has understood the information sheet and is willing to
give informed written consent to participate in the study, and that the patient
understands that it is their right to withdraw from the trial at any time without
prejudice to their future treatment.
Project milestones Based upon the average number of patients seen in general surgical clinics
with symptomatic inguinal hernias requiring surgical intervention, we envision recruitment
taking 6-8 months across both sites.
Taking an average waiting time of 3 months from clinic appointment to date of operation, most
patients in the trial should have their planned intervention by 9-12 months from start of
recruitment.
Most of the key outcomes will be collected within 6 weeks post procedure. The most important
outcomes of chronic pain and early recurrence will be evaluated at 3, 12 month follow-up post
procedure, hence taking between 18-24 months for completion of trial.
The effect sizes used for sample size calculation were conservative and the true required
sample may be lower. An interim analysis will be performed after recruitment of 25 patients
per group. This data will help to guide the requirement for further recruitment and establish
if intergroup differences are larger than expected. It may be possible to curtail recruitment
with a lower sample size.
Risk Profile It is not likely that there should be any reason to stop this trial prematurely,
as the interventions in question are currently in regular clinical practice both in the NHS
and worldwide without any added risks reported by the manufacturers or in the scientific
literature.
Intervention; Both treatment techniques of laparoscopic fixation of mesh with stapling device
and use of self-gripping mesh not requiring fixation are used already for treatment of
inguinal hernias, both within the NHS and across the world. They have been shown to be safe
and effective, with no more increase in complications. Treatment related risks will be
covered by NHS indemnity.
Complications are classed as:
Non-specific: Acute post-operative pain, infection, haematoma, recurrence, port site hernia.
Specific complications: Chronic post-operative pain, shrinkage; dislocation; migration;
erosion of mesh All procedures will be planned and performed by Consultant Surgeons skilled
and experienced in the performance of laparoscopic inguinal hernia mesh repair. Complications
and adverse events will be reported to the Principal Investigator and each incidence
individually investigated. Any concerns over outcomes will be discussed with all of the
co-investigators and clinicians involved in the trial. Any safety concerns will result in
suspension of the trial pending further investigation.
Trial Process; All of the trial outcomes are non-invasive and offer no significant risk to
patients; in fact the enhanced follow-up will allow closer monitoring of patients for
procedure or product related complications.
The participants will have given their informed consent, prior to taking part in this study.
All participant details will be number coded and kept securely. Participants are unlikely to
be identified from digital images, which will be numbered to ensure anonymity and archived
securely.
The overall aim is to observe and compare outcomes in patients undergoing standardised,
established treatment protocols currently in wide utilisation, with no deviation from
standard practice. As such investigators do not envisage patients being placed at undue risk.
