Comparative Evaluation of MEBO Ointment and Topical Diltiazem Ointment in the Treatment of Acute Anal Fissure: a Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 183
- 试验地点
- 1
- 主要终点
- Change in Pain Score
研究概览
简要总结
No study to date has compared topical DTZ to MEBO ointment in the treatment of anal fissure. Therefore, the present study aims to compare the efficacy and safety of DTZ to MEBO in the treatment of acute anal fissure. The investigators propose to conduct a comparative randomized clinical study. In this study, the investigators will compare patients with acute anal fissure receiving MEBO ointment vs Topical DTZ ointment vs a combination of MEBO and DTZ ointment.
Hypothesis:
MEBO in combination with DTZ is more effective than DTZ or MEBO alone in the treatment of acute anal fissure.
详细描述
Trial Design: This trial is designed as a 1:1:1 randomized, controlled, parallel design. The primary endpoints are change in pain score and wound healing from baseline to 1 week from the study start date; secondary endpoints are change in pain score and wound healing at 6 and 10 weeks from the study start date, defecation strain score & the patient's global impression of improvement at 10 weeks.
Assessments & Visits: The patient will be assessed for pain, wound healing, strain during defecation, impression of improvement, & adverse events at weeks 1, 6 & 10 after the study start date. Trained resident or research assistant (RA) will administer the questionnaires on pain score, strain during defecation, & patient's global impression of improvement. During the follow-up visits, the average score for each of the pain & defecation strain scores will be taken for the 3 most recent days that the patient has defecated. The patient will be given a paper diary to record the pain score & strain score during defecation 3 days prior to the follow-up clinic visit.
Sample Size: The investigators will design this superiority trial as three-arm trials, where one arm is Diltiazem, second is MEBO, & last is a combination of both. Assuming that the pain score difference between both treatments will be 0.5 points with a 1-point standard deviation on the numeric rating scale (5 for DTZ & 3 for combination arm DTZ & MEBO), & using an alpha of 0.05 & a power of 80%, a sample size of 47 patients in each arm is needed. After accounting for a 30% loss to follow up, 61 patients will need to be recruited in each arm. The total number of patients to be recruited in the three arms is 183 patients.
Recruitment: At the American University of Beirut Medical Center, patients with acute anal fissure are treated at the outpatient center (private & outpatient clinics) of the hospital by all the general surgeons. The patients will be introduced to the study by their attending physician. If the patient agrees to participate, the RA (part of the research team) will approach & screen the patient according to the defined inclusion & exclusion criteria. If the patient is found eligible for the study, the RA will discuss the study & obtain his/her informed consent. The expected recruitment rate is 4 patients/week. The first 2 visits of the patient to the clinic at weeks 1 &6 from the start date of the study are part of clinical care & the patient will not be reimbursed for these visits. The last visit to the clinic that will take place at week 10 will be for follow-up as part of the research, so the patient and physician will be reimbursed for transportation and professional fees, respectively, by the research grant.
ASSIGNMENT OF INTERVENTIONS
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
The physician and the patient will not be blinded to the allocation, but the rest of the study team will be blinded. We will blind to allocation the physician who will assess for outcomes, and the research assistants who are collecting the data, data analysts.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be 18 years and above.
- •Subjects with 3 months (90 days) or less history of painful anal fissure (AF), prior to screening, where AF-related pain-associated with, or following, defecation is experienced at least twice a week during the symptomatic phase, with pain scores at an average of ≥ 3 on an 11-point NRS (Numerical Rating Scale, range 0-10 where 0 = no pain and 10 = worst pain imaginable).
- •Subjects with an average of ≥4 on an 11-point NRS during the screening phase for worst anal pain associated with, or following, defecation for the most recent 3 days on which the subject has defecated.
- •Subjects with evidence of a radial fissure, with induration at the edges, seen on anal examination.
- •Willing to stop all other concomitant topical preparations applied perianally prior to commencing study treatment, and throughout the study. There will be a "washout" period of at least 2 weeks prior to commencing the study for subjects who were using other concomitant topical preparations applied perianally.
- •Able to give consent
排除标准
- •Subjects unwilling to be examined for AF.
- •Subjects who have undergone the following procedures:
- •Lateral sphincterotomy or anal stretch or other previous surgery involving the anal canal or perianal region (hemorrhoidectomy, anal fistula surgery).
- •Incision of perianal abcess.
- •Subjects who have had sub-fissure injection of botulinum toxin within 6 months period prior to screening, or have used glyceryl trinitrate (GTN) ointment for >1 week in the 4 weeks prior to the screening visit.
- •Subjects with AF associated with other conditions (drug-induced [e.g. nicorandil], trauma, HIV infection, fistula-in-ano, inflammatory bowel disease, perianal sepsis or malignancy).
- •Subjects with cardiovascular disease
- •Subjects with known hypersensitivity to DTZ or the ingredients of MEBO (Sesame oil)
- •Subjects taking medications prohibited by the protocol.
- •Subjects who have taken experimental agents must have been discontinued at least 8 weeks prior to screening, or for a period equivalent to 5 half-lives (t1/2) of the agents.
- •Subjects who have the following gastrointestinal disorders:
- •Inflammatory bowel disease.
- •Chronic faecal incontinence.
- •History of radiation therapy to the pelvis.
- •Fixed anal stenosis/fibrosis.
- •Subjects with major psychiatric (including drug or alcohol abusers), or haematological illness. (diseases of the vascular system; source: )Subjects with planned elective or other treatment requiring hospitalization, during the study, booked before entry into the study.
- •Subjects who will be unavailable for the duration of the trial, likely to be noncompliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason.
- •Patients who are taking oral therapy for anal fissure will also be excluded from the study.
研究组 & 干预措施
DTZ arm
The first group of patients will apply MEBO ointment peri-anally 3 times daily for 6 weeks.
干预措施: Mebo (Drug)
MEBO arm
The second group of patients will apply topical DTZ ointment peri-anally 3 times daily for 6 weeks.
干预措施: Diltiazem (Drug)
MEBO and DTZ arm
The third group will apply a combination of MEBO and DTZ ointment peri-anally 3 times daily for 6 weeks. Those who fail therapy (meaning they report no pain improvement after two weeks of treatment) from either the MEBO or the Diltiazem arm will be switched to the combination arm. If they also fail to improve after two weeks on the treatment arm, then they will be offered surgery. If the patient refuses to switch to the combination arm and wishes to proceed to surgery immediately, then the patient will be directed to surgery.
干预措施: Diltiazem (Drug)
MEBO and DTZ arm
The third group will apply a combination of MEBO and DTZ ointment peri-anally 3 times daily for 6 weeks. Those who fail therapy (meaning they report no pain improvement after two weeks of treatment) from either the MEBO or the Diltiazem arm will be switched to the combination arm. If they also fail to improve after two weeks on the treatment arm, then they will be offered surgery. If the patient refuses to switch to the combination arm and wishes to proceed to surgery immediately, then the patient will be directed to surgery.
干预措施: Mebo (Drug)
结局指标
主要结局
Change in Pain Score
时间窗: Baseline to 1 week from the start date of the study
Pain is evaluated through the Numerical Rating Scale, range 0-10 where 0 = no pain and 10 = worst pain imaginable
Wound Healing
时间窗: At 1 week from that start date of the study
Wound healing is assessed through physical examination: digital rectal examination is not done in case of painful anal fissure. Assessment for wound healing will be performed by the treating physician of the patient. The patient will be asked to strain to make the anal fissure more visible. If it is difficult to see on physical examination, digital rectal exam is done carefully. The degree of healing will be reported as none, partial or complete.
次要结局
- Change in Pain Score(At 6 and 10 weeks from the start date of the study)
- Wound Healing(At 6 and 10 weeks from the start date of the study)
- Defecation Strain Score(At 1 week, 6 weeks, and 10 weeks from that start date of the study)
- Global Impression of Improvement(At 1 week, 6 weeks, and 10 weeks from that start date of the study)
研究者
Eman Sbaity
Instructor of Surgery
American University of Beirut Medical Center