Clinical Trial Verifying C-REX LapAid and C-REX DMH/DMHC
Condition: Cancer Colon; Polyp of Colon
MeSH terms: Colonic Polyps
Study type: Interventional

Summary: 
      In colorectal surgery, hand suturing and stapling are routine methods for performing
      intestinal anastomoses, and these methods appear to be similar in terms of clinical safety.
      Despite several years of experience with surgical procedures as well as improvements to the
      medical devices, problems with disturbed anastomotic healing leading to leakage and stenosis
      after colorectal surgery remain a significant challenge for surgeons. In addition,
      preoperative radiotherapy has been shown to increase the risk of anastomotic leakage even
      further.

      The methods that are used today to detect leakages are unfortunately inaccurately and limited
      to monitoring symptoms, temperature, CRP (C-reactive protein)-levels, and performing
      abdominal examinations and CT-scans. These clinical signs and parameters usually become
      apparent several days after onset of the leakage, which leads to a delayed diagnosis.
      Anastomotic leakage is not only a significant cause of increased morbidity of complications
      and mortality in patients, but also associated with increased risk of local recurrence and
      poor prognosis. Moreover, when reoperation is required to fix the leakage, a permanent stoma
      may be made at the level of the sigmoid colon and this procedure impacts quality of life
      negatively.

      Based on the above considerations, a novel, adaptive anastomotic method has been developed by
      CarpoNovum to achieve a safer anastomosis. The method's working name is C-REX Ring-locking
      Procedure (C-REX is referred to our Colorectal anastomotic rings for Re-join the intestinal
      ends and validate the anastomosis, with function of Extract samples for analysis and conduct
      X-ray through connected catheters).

      The novel adaptive anastomotic medical devices, C-REX LapAid and C-REX DMH/DMHC are easy to
      use, with unique possibility to control the anastomosis during and after surgery. The
      previous successful preclinical study encourages a clinical verification in patients
      undergoing colonic resection to evaluate the safety and performance of C-REX Ring-locking
      Procedure by use of C-REX LapAid and C-REX DMH/DMHC.
    

Detailed description: 
      OVERALL DESIGN The study is a prospective, multicenter, single arm study Possible study
      candidates are patients requiring resection of the left colon (descending colon and sigmoid)
      or the upper rectum (15cm above the anal rim) due to malign or benign disease. After physical
      examination, checking of inclusion/exclusion criteria, and after informed consent has been
      achieved, potential subjects will be enrolled in the study, and the investigational surgery
      will be performed during hospitalization. The devices, i.e. C-REX LapAid and C-REX DMH/DMHC
      (dual male handle/dual male catheter handle), included in C-REX Ring-locking Procedure are
      applied to the inside of the intestine and connected to catheters that allow monitoring of
      the anastomosis (if DMC is applied).

      The healing period is expected to be approximately 10 ± 2 days. The short-term implant, i.e.
      the anastomotic ring, detaches via necrosis on the inner part of the intestinal surface and
      is expelled the natural way during hospitalization.

      The subject can be discharged from the hospital when the short-term implant has been
      evacuated, and the subject has begun to eat and has normal bowel movements. The observation
      period lasts until 30 days after surgery. The subject then continues follow-up according to
      local routine.

      QUALITY CONTROL Authorization to perform C-REX Ring-locking Procedure According to
      CarpoNovum's regulation (Document 0041: Procedure, Accreditation of Surgeons for Clinical
      Studies), clinical investigators must be authorized to conduct the C-REX Ring-locking
      Procedure with C-REX LapAid and C-REX DMH/DMHC by performing at least one surgery on pigs and
      at least one train-in surgery on patients with the person in charge of the study (Dr. Anders
      Grönberg). When the clinical investigator is authorized to perform the C-REX Ring-locking
      Procedure with C-REX LapAid System, he or she receives a certificate. This certificate could
      also admit the clinical investigator the right to authorize other surgeons to perform C-REX
      Ring-locking Procedure with C-REX LapAid and C-REX DMH/DMHC (i.e. to perform at least one
      operations on pigs and at least one train-in operations on patients with the authorized
      clinical investigator).

      Monitoring To ensure that the study is appropriately conducted, a monitor appointed by the
      sponsor will visit the investigation site regularly and oversee the investigator's compliance
      with the CIP, perform source-data verification and report to the sponsor on the progress of
      the study.

      Each investigation site and clinical investigator in the study will be monitored. On all
      occasions, the responsible monitor and/or the person in charge of the study will secure for
      example that:

        1. Compliance with CIP (clinical investigation plan) is maintained and any deviation from
           CIP is discussed with the clinical investigators, documented and reported to the
           sponsor; if the changes are significant, the competent authority and the ethical
           committee will be informed;

        2. The device is being used according to CIP, IB (investigator's brochure) and IFU
           (instructions for use), and if modifications are required either to the device or its
           method of use or to the CIP, this need shall be reported to the sponsor;

        3. Signed and dated informed consent forms have been obtained from each subject at the time
           of enrollment and before any study-related procedures are undertaken;

        4. The data in CRFs (case report forms) are complete, are recorded in a timely manner and
           are consistent with the source data;

        5. Traceability and device accountability of the investigational device are properly
           maintained;

        6. Maintenance and calibration of equipment relevant for assessment of the study is
           performed;

        7. Possible adverse events or device deficiencies have been properly documented and
           reported;

        8. Subjects withdrawal and/or non-compliance is documented and discussed with the clinical
           investigator and reported to the sponsor;

        9. Clinical investigators have and continue to have staff and facilities to conduct the
           study safely and effectively;

       10. Clinical investigators have and continue to have access to an adequate number of
           subjects and the investigational device to complete the study.

      The responsible monitor will write a report after each visit to the medical institutions. The
      reports will be sent to the sponsor and the principal clinical investigators.

      Documentation and data processing Medical record of subjects

      The following information should be clearly documented in medical record of subjects:

        -  That the subject is informed about the study and that the subject has signed the
           informed consent forms.

        -  That the subject is participating in the study; the identification code for the subject,
           the name of the study, and the study number (i.e., CREX-003).

        -  Which treatment the study refers to (i.e., C-REX Ring-locking Procedure with use of
           C-REX LapAid and C-REX DMH/DMHC).

        -  Name of the principal clinical investigator.

        -  All AEs (adverse events) and device deficiencies.

      Document and data control Prior to commencement of the study, clinical investigators and
      their staff will be informed about CIP, CRFs and other study documents and procedures.

      For each subject enrolled, regardless of medical device initiation, a CRF must be completed
      and signed by corresponding investigation personnel. This applies to those subjects who fail
      to complete the study. If a subject withdraws from the study, the reason must be noted on
      CRF.

      Data and information of subjects derived from the study are considered as source data. To
      ensure that all data are complete and correct, source data verification (SDV) will be
      confirmed by the monitor.

      Comments in CRF should be made with a ballpoint pen with permanent ink. If comments are
      missing in CRF, reasons for this must be stated. No questions, squares, fields or similar
      should be left without comments.

      CRF entries and corrections will only be performed by investigational personnel, authorized
      by the principle clinical investigator. Errors should be crossed out but not obliterated, the
      correction inserted, and the change initialed and dated by the clinical investigator.

      Then entries will be checked by the monitor and any errors or inconsistencies will be checked
      and corrected immediately.

      The responsible clinical investigator is obliged to keep the subject identification lists
      with the subject's identification code and identity in a safe place at the investigation site
      (hospital), accessible only to the investigation personnel. These source data and subject
      identification lists will be saved for 10 years after the close of the study at the medical
      institution.

      NUMBER OF SUBJECTS The aim of this study is to verify the novel device in clinical practise
      and for CE (Conformité Européenne) marking later. Since no control group is included, there
      is no need for power determinations.

      Considering that similar anastomotic devices have been used in clinic for decades, 20
      subjects will be included in The First Affiliated Hospital of Xiamen University.

      STATISTICAL ANALYSIS OF VARIABLES Descriptive methods are used to analyze the data collected
      in the study. The incidences of anastomotic leakage and other AEs/device deficiencies are
      calculated.
    

Intervention name(s): C-REX Ring-locking Procedure
Intervention type(s): Device
Intervention description(s): The C-REX Ring-locking Procedure is a method based on adaptive anastomosis, in which intestinal ends adapt to each other after resection due to tumor, injury, or other disease.
The investigational devices comprised of two components, i.e. C-REX LapAid and C-REX DMH/DMHC
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment