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出境医 / 临床实验 / Optimal Timing for Performing Loop Electrosurgical Excision Procedure

Optimal Timing for Performing Loop Electrosurgical Excision Procedure

Study Description
Brief Summary:

Cervical precancerous lesions (cervical intraepithelial neoplasia) are frequently diagnosed and treated in women of reproductive-aged [1]. Loop electrosurgical excision procedure (LEEP) is the standard surgical treatment in CIN 2 or 3 [1]. This procedure is an inexpensive, easy to learn and provide specimens for pathological examination with the least major surgical morbidity [2].

Although LEEP is a safe procedure, complications such as postoperative bleeding have been reported. These haemorrhages make patients anxious, undergo unnecessary follow-ups, additional procedures to stop bleeding and interfere in patients daily activities. Various interventions have been attempted to prevent and/or reduce perioperative and/or postoperative haemorrhage after LEEP including vasopressiın, tranexamic acid, Monsel's solution, or local hemostats (TochoSil or Tisseel), but have failed to show a definite advantage over routine practice [2-4].

A hormonal variation during the menstrual cycle is known to affect hemostasis [5] and the blood flow of the genital organ [6,7]. A systematic review of the literature through PubMed, OvidSP, Google Scholar, and Scopus identified only one previous investigation of menstrual cycle period affect blood loss during the LEEP procedure. The authors showed that women had less perioperative bleeding during the follicular phase than during the luteal phase [8]. Two retrospective studies have also demonstrated rhinoplasty and mammoplasty caused more bleeding during the luteal phase and menstruation than during the follicular phase [9,10]. In contrast, other retrospective studies have shown no relation between operative blood loss and the menstrual cycle for hysterectomy, myomectomy, and ovarian cystectomy [11-13] To answer this clinically relevant question, the investigators performed a randomized study comparing perioperative and postoperative bleeding between patients underwent LEEP procedure during the follicular or luteal phase of the menstrual cycle.


Condition or disease Intervention/treatment Phase
Cervical Precancerous Lesions Other: Vaginal bleeding Not Applicable

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Optimal Timing for Performing Loop Electrosurgical Excision Procedure According to Different Menstrual Phase: Which is Best?
Actual Study Start Date : May 20, 2019
Actual Primary Completion Date : September 18, 2019
Actual Study Completion Date : September 18, 2019
Arms and Interventions
Arm Intervention/treatment
follicular phase group
The menstrual dates of patients were normalized to a 28-day cycle with the following formula: adjusted day of the menstrual cycle = (14 X day of the cycle at the time of surgery) / (cycle length of the patient - 14). In light of this formula patients were classified into the follicular phase group (defined as <15 adjusted days, group A).
Other: Vaginal bleeding
Vaginal bleeding was classified into four categories according to the timing. Intraoperative bleeding (defined as bleeding that occur during the LEEP procedure), early postoperative bleeding (defined as bleeding that occur between end of the LEEP procedure and home discard), late postoperative bleeding (defined as bleeding that occur within two weeks after the home discard, and required hemostatic interventions such as electrocauterization, gauze packing, or cervical suturing, excluding menstrual bleeding), and persistent postoperative bleeding (defined as vaginal bleeding that occurs more than 2 weeks after the procedure with or without required hemostatic interventions, excluding menstrual bleeding).

luteal phase group
The menstrual dates of patients were normalized to a 28-day cycle with the following formula: adjusted day of the menstrual cycle = (14 X day of the cycle at the time of surgery) / (cycle length of the patient - 14) [14]. In light of this formula, patients were classified into the luteal phase group (defined as ≥15 adjusted days, group B).
Other: Vaginal bleeding
Vaginal bleeding was classified into four categories according to the timing. Intraoperative bleeding (defined as bleeding that occur during the LEEP procedure), early postoperative bleeding (defined as bleeding that occur between end of the LEEP procedure and home discard), late postoperative bleeding (defined as bleeding that occur within two weeks after the home discard, and required hemostatic interventions such as electrocauterization, gauze packing, or cervical suturing, excluding menstrual bleeding), and persistent postoperative bleeding (defined as vaginal bleeding that occurs more than 2 weeks after the procedure with or without required hemostatic interventions, excluding menstrual bleeding).

Outcome Measures
Primary Outcome Measures :
  1. mean early postoperative blood loss [ Time Frame: 6 hours ]
    Estimated early postoperative blood loss was calculated using the difference in hematocrit values taken after LEEP procedure and 6 hours after procedure, according to the following formula: Estimated Blood Loss = estimated blood volume X (hematocrit 1 - hematocrit 2)/hematocrit 1, where the estimated blood volume in milliliters = woman's weight in kilograms X 85


Secondary Outcome Measures :
  1. mean intraoperative bleeding [ Time Frame: During the LEEP procedure ]
    The volume of intraoperative blood loss was measured by weighing a gauze sponge during the procedure. Because it is important to collect the blood accurately, we used a specially designed operating gauze sponge and an electronic scale to weigh all the material (with a 1-g deviation range). The LEEP procedure was performed ensuring that all blood lost during the procedure was absorbed with gauzes. We took care to clean all the bleeding with gauze obtained during the procedure.

  2. the rate of late postoperative bleeding [ Time Frame: bleeding that occur within four weeks after the home dischard ]
    late postoperative bleeding (defined as bleeding that occur within four weeks after the home dischard, and required hemostatic interventions such as electrocauterization, gause packing, or cervical suturing, excluding menstrual bleeding).


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Women was ≥ 21 years old
  2. Women was not pregnant
  3. Women were not menstruating or menopausal status
  4. Women with the normal regular menstrual cycle (defined as an interval between 21 and 35 days and duration between 3 and 10 days)
  5. Women had one of the following indications for LEEP procedure

    1. a histology-proven, persistent, low grade squamous intraepithelial lesions (LGSIL),
    2. a histology-proven high-grade squamous intraepithelial lesions (HGSIL),
    3. discrepancies between cytological reports and colposcopic impressions,
    4. investigation for unsatisfactory colposcopy,
    5. micro invasion or adenocarcinoma in situ on cervical punch biopsy

Exclusion Criteria:

  • Women with cervical or vaginal infection,
  • Women with the abnormal menstrual cycle,
  • Women taking any medication (or injection) such as oral contraceptives, GnRH agonist, medroxyprogesterone acetate, or anticoagulants
  • Women with coagulation defect,
  • Women with mental incapacity,
  • Women with a history of neurologic deficit,
  • Women with previous hysterectomy with removal of the cervix,
  • Women with a history of cervical cancer
Contacts and Locations

Locations
Layout table for location information
Turkey
Kemal Gungorduk
Muğla, Turkey, 35460
Sponsors and Collaborators
Erzincan Military Hospital
Tracking Information
First Submitted Date  ICMJE May 12, 2019
First Posted Date  ICMJE May 16, 2019
Last Update Posted Date October 15, 2019
Actual Study Start Date  ICMJE May 20, 2019
Actual Primary Completion Date September 18, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
mean early postoperative blood loss [ Time Frame: 6 hours ]
Estimated early postoperative blood loss was calculated using the difference in hematocrit values taken after LEEP procedure and 6 hours after procedure, according to the following formula: Estimated Blood Loss = estimated blood volume X (hematocrit 1 - hematocrit 2)/hematocrit 1, where the estimated blood volume in milliliters = woman's weight in kilograms X 85
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • mean intraoperative bleeding [ Time Frame: During the LEEP procedure ]
    The volume of intraoperative blood loss was measured by weighing a gauze sponge during the procedure. Because it is important to collect the blood accurately, we used a specially designed operating gauze sponge and an electronic scale to weigh all the material (with a 1-g deviation range). The LEEP procedure was performed ensuring that all blood lost during the procedure was absorbed with gauzes. We took care to clean all the bleeding with gauze obtained during the procedure.
  • the rate of late postoperative bleeding [ Time Frame: bleeding that occur within four weeks after the home dischard ]
    late postoperative bleeding (defined as bleeding that occur within four weeks after the home dischard, and required hemostatic interventions such as electrocauterization, gause packing, or cervical suturing, excluding menstrual bleeding).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Optimal Timing for Performing Loop Electrosurgical Excision Procedure
Official Title  ICMJE Optimal Timing for Performing Loop Electrosurgical Excision Procedure According to Different Menstrual Phase: Which is Best?
Brief Summary

Cervical precancerous lesions (cervical intraepithelial neoplasia) are frequently diagnosed and treated in women of reproductive-aged [1]. Loop electrosurgical excision procedure (LEEP) is the standard surgical treatment in CIN 2 or 3 [1]. This procedure is an inexpensive, easy to learn and provide specimens for pathological examination with the least major surgical morbidity [2].

Although LEEP is a safe procedure, complications such as postoperative bleeding have been reported. These haemorrhages make patients anxious, undergo unnecessary follow-ups, additional procedures to stop bleeding and interfere in patients daily activities. Various interventions have been attempted to prevent and/or reduce perioperative and/or postoperative haemorrhage after LEEP including vasopressiın, tranexamic acid, Monsel's solution, or local hemostats (TochoSil or Tisseel), but have failed to show a definite advantage over routine practice [2-4].

A hormonal variation during the menstrual cycle is known to affect hemostasis [5] and the blood flow of the genital organ [6,7]. A systematic review of the literature through PubMed, OvidSP, Google Scholar, and Scopus identified only one previous investigation of menstrual cycle period affect blood loss during the LEEP procedure. The authors showed that women had less perioperative bleeding during the follicular phase than during the luteal phase [8]. Two retrospective studies have also demonstrated rhinoplasty and mammoplasty caused more bleeding during the luteal phase and menstruation than during the follicular phase [9,10]. In contrast, other retrospective studies have shown no relation between operative blood loss and the menstrual cycle for hysterectomy, myomectomy, and ovarian cystectomy [11-13] To answer this clinically relevant question, the investigators performed a randomized study comparing perioperative and postoperative bleeding between patients underwent LEEP procedure during the follicular or luteal phase of the menstrual cycle.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Cervical Precancerous Lesions
Intervention  ICMJE Other: Vaginal bleeding
Vaginal bleeding was classified into four categories according to the timing. Intraoperative bleeding (defined as bleeding that occur during the LEEP procedure), early postoperative bleeding (defined as bleeding that occur between end of the LEEP procedure and home discard), late postoperative bleeding (defined as bleeding that occur within two weeks after the home discard, and required hemostatic interventions such as electrocauterization, gauze packing, or cervical suturing, excluding menstrual bleeding), and persistent postoperative bleeding (defined as vaginal bleeding that occurs more than 2 weeks after the procedure with or without required hemostatic interventions, excluding menstrual bleeding).
Study Arms  ICMJE
  • follicular phase group
    The menstrual dates of patients were normalized to a 28-day cycle with the following formula: adjusted day of the menstrual cycle = (14 X day of the cycle at the time of surgery) / (cycle length of the patient - 14). In light of this formula patients were classified into the follicular phase group (defined as <15 adjusted days, group A).
    Intervention: Other: Vaginal bleeding
  • luteal phase group
    The menstrual dates of patients were normalized to a 28-day cycle with the following formula: adjusted day of the menstrual cycle = (14 X day of the cycle at the time of surgery) / (cycle length of the patient - 14) [14]. In light of this formula, patients were classified into the luteal phase group (defined as ≥15 adjusted days, group B).
    Intervention: Other: Vaginal bleeding
Publications * Paraskevaidis E, Davidson EJ, Koliopoulos G, Alamanos Y, Lolis E, Martin-Hirsch P. Bleeding after loop electrosurgical excision procedure performed in either the follicular or luteal phase of the menstrual cycle: a randomized trial. Obstet Gynecol. 2002 Jun;99(6):997-1000.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 15, 2019)
75
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 18, 2019
Actual Primary Completion Date September 18, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Women was ≥ 21 years old
  2. Women was not pregnant
  3. Women were not menstruating or menopausal status
  4. Women with the normal regular menstrual cycle (defined as an interval between 21 and 35 days and duration between 3 and 10 days)
  5. Women had one of the following indications for LEEP procedure

    1. a histology-proven, persistent, low grade squamous intraepithelial lesions (LGSIL),
    2. a histology-proven high-grade squamous intraepithelial lesions (HGSIL),
    3. discrepancies between cytological reports and colposcopic impressions,
    4. investigation for unsatisfactory colposcopy,
    5. micro invasion or adenocarcinoma in situ on cervical punch biopsy

Exclusion Criteria:

  • Women with cervical or vaginal infection,
  • Women with the abnormal menstrual cycle,
  • Women taking any medication (or injection) such as oral contraceptives, GnRH agonist, medroxyprogesterone acetate, or anticoagulants
  • Women with coagulation defect,
  • Women with mental incapacity,
  • Women with a history of neurologic deficit,
  • Women with previous hysterectomy with removal of the cervix,
  • Women with a history of cervical cancer
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Turkey
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03952975
Other Study ID Numbers  ICMJE MUGLA SKU
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kemal GUNGORDUK, Erzincan Military Hospital
Study Sponsor  ICMJE Erzincan Military Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Erzincan Military Hospital
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP