D-PLEX 312 - Phase III, Prospective, Multinational, Multicenter, Randomized, Controlled, Two-arm, Double Blind Study to Assess Efficacy and Safety of D-PLEX In Prevention of Post Abdominal Surgery Incisional Infection (SHIELD II)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- PolyPid Ltd.
- 入组人数
- 975
- 试验地点
- 109
- 主要终点
- To assess the anti-infective efficacy of D-PLEX over a period of 30 days post operation, by preventing surgical site infection (SSI), defined as superficial and deep infection, in the target incision(s), compared to the SoC treated control.
研究概览
简要总结
Phase III, Prospective, Multinational, Multicenter, Randomized, Controlled, Two-arm, Double Blind Study to Assess Efficacy and Safety of D-PLEX Administered Concomitantly with the Standard of Care (SoC), Compared to a SoC Treated Control Arm, in Prevention of Post Abdominal Surgery Incisional Infection.
详细描述
D-PLEX is a new formulation of extended controlled release of Doxycycline in the applied area for about 30 days. This study is aimed to assess the safety and efficacy of D-PLEX in prevention of post abdominal surgery incisional infection.
The study population includes male and female, 18 years old and above at screening, undergoing an elective colorectal surgery involving colon or rectal resection, with or without a stoma formation, that includes at least 1 incision that is > 20cm (target incision).
Eligible and willing subjects will be randomly allocated into 2 blinded study arms, either to the investigational arm (D-PLEX + SoC) or to the control arm (SoC only) in a 1:1 ratio. Subjects will be stratified by type of prophylactic SoC (IV antibiotic only, IV antibiotic with mechanical bowel preparation or IV antibiotic with oral antibiotics combined with mechanical bowel preparation) and by region (US versus Europe + Israel).
D-PLEX will be applied during the surgery at the final stage of incision closure. All patients will be followed up for additional 5 visits over 2 months, for safety and incisional wound assessment. This will include blood tests for hematology and chemistry as well as physician's assessment of the incisional wound.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This is a double-blind clinical trial. The sponsor, the subjects, outcomes assessor and all staff involved in the collection and recording of the clinical and laboratory data, based on which the independent adjudication committee will perform their assessment, will be blind to treatment assignment. In addition, all aspects of data management and clean-up will be done in blinded datasets.
The study site personnel, who perform the index surgery (Operation room staff), will be trained not to disclose the treatment arm to the blinded Investigator, to the subject, his/her family, to other health care providers not present during the surgery or to the study Sponsor representatives. Wound assessment throughout the study follow-up visits will be done by a blinded Investigator, that will not be involved in the surgery. An emergency card containing the Study Name, NIH number, Center Name/number, PI's name and contact details will be provided to the subjects.
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects undergoing an elective colorectal surgery involving resection, with or without a stoma formation, that includes at least 1 abdominal incision that is >20cm (target incision).
- •Subjects are preoperative hemodynamically stable. (BP≤180/110 and >90/60 mmHg, and HR≤120 and >60 bpm, and temperature ≤37.50C and >35.50C).
- •Male or non-pregnant female.
- •Female of child-bearing potential should have a negative pregnancy test (serum or urine dipstick) prior to index procedure.
- •Subjects' age 18 years old and above at screening.
- •Subjects who sign the written Informed Consent Form.
- •Subjects who are willing and able to participate and meet all study requirements.
- •Survival expectancy of at least sixty days post randomization.
排除标准
- •Subjects with suspected/diagnosed intestinal perforation, intra-abdominal abscess, or any emergency/urgent colorectal surgery with acute intestinal obstruction (ex. toxic colitis, ileus/sub-ileus, megacolon, diverticulitis, volvulus, etc.)
- •Subjects who underwent an intra-abdominal surgery within the last six months prior to randomization.
- •Subjects with any preoperative active infection or who are receiving any antibiotic therapy in the past one week prior to randomization, excluding pre-operative prophylaxis or antibiotics for the treatment of the disease that is the indication for surgery.
- •Subjects undergoing concomitant major procedures in addition to the colorectal resection. Female sterilization surgeries (i.e. salpingo-oophorectomy etc.), involvement of a small bowel procedure or cholecystectomy may be allowed, pending an advanced consultation and approval from the Sponsor.
- •Subjects who received any anti-cancer treatment within the last four weeks of surgery.
- •Subjects who received radiation for colorectal cancer to the abdomen and/or pelvis area, within the last four weeks of the planned abdominal surgery.
- •Subjects who received oral or IV Doxycycline or Tetracycline family antibiotics during the past four weeks prior to randomization.
- •Subjects with known allergy to Doxycycline and/or to the tetracycline family of drugs or to the D-PLEX's excipients.
- •Subjects with known allergies to more than three substances.
- •Subjects with history of severe allergic reaction to any substance, having required treatment with intravenous steroids/intramuscular epinephrine, or who in the opinion of the PI is at high risk of developing severe allergic reactions.
- •Uncontrolled medical condition.
- •Subjects who underwent any abdominal surgery and current planned index surgery involves re-opening the scar of a prior abdominal surgery performed within the last three years.
- •Any subject with an active malignancy or with malignancy that has not been in complete clinical remission and without maintenance chemo or immunotherapy for at least three years.
研究组 & 干预措施
Standard of Care
The SoC for prophylactic antibiotic treatment is based on international guidelines
干预措施: Standard of Care (SoC) (Other)
D-PLEX+SoC
D-PLEX is provided as an adjunct to the SoC treatment
干预措施: Standard of Care (SoC) (Other)
D-PLEX+SoC
D-PLEX is provided as an adjunct to the SoC treatment
干预措施: D-PLEX (Drug)
结局指标
主要结局
To assess the anti-infective efficacy of D-PLEX over a period of 30 days post operation, by preventing surgical site infection (SSI), defined as superficial and deep infection, in the target incision(s), compared to the SoC treated control.
时间窗: By day 30 post surgery
Infection rate as measured by the proportion of subjects with at least one abdominal incisional infection event, as determined by a blinded and independent adjudication committee, within 30 days post abdominal surgery. \[abdominal incisional infection is composed of Deep Incisional Surgical Site Infection (DSSI) and Superficial Incisional Surgical Site Infection (SSSI)\].within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee. All-cause mortality and re-interventions in the target incision within 30 days post index surgery will be analysed as treatment failure. Incisional infection event only, occurred within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee. \[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)\].
Safety of D-PLEX in Prevention of Post Abdominal Surgery
时间窗: By day 60 post surgery
Safety parameters will be evaluated by adverse events
Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional
时间窗: By day 60 post surgery
Incisional wound healing will be assessed by a blinded Investigator, using a visual examination as well as Modified Vancouver Scar Scale wound assessment questionnaires. The questionnaire has a numeric scale from 0-4 in Vascularity, Pigmentation, Pliability and height
Infection Rate as Measured by the Percentage of Subjects With SSI Event in the Target Incision Within 30 Days Post Index Surgery or Re-interventions or Death [for Any Reason] in the Population of Subjects With Target Incision Length >20 cm
时间窗: By day 30 post surgery
The primary analysis is based on a composite treatment-failure (Yes/No) variable, indicating if a subject had at least one treatment-failure event, defined as follows: SSI, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee, death (from any reason) or re-intervention at the target incision site within 30 days post surgery will be considered a treatment failure for the primary ITT analysis.
次要结局
- Assessment of Infection rate in patient undergoing abdominal colon surgery(At study visits: day 1, day 5, day 14 and day 30 post surgery)
- The Percentage of Subjects With at Least One SSI Event in the Target Incision(By day 30 post surgery)
- Infection Rate as Measured by the Percentage of Subjects With SSI Event in the Target Incision Within 30 Days Post Index Surgery or Re-interventions or Death [for Any Reason] in the Population of Subjects With Target Incision Length >7 cm(30 days post surgery)
- Percentage of Subjects With at Least 1 Score of ASEPSIS> 20, Within 30 Days Post Abdominal (Index) Surgery(30 days post surgery)