A Phase III Placebo-Controlled, Randomized Three-Arm Study of Doxepin and a Topical Rinse in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 275
- 试验地点
- 348
- 主要终点
- Mean Area Under the Curve (AUC) of Total Pain Reduction
研究概览
简要总结
The purpose of this study is to test whether a mouthwash made with a drug called doxepin can reduce the pain caused by mouth sores resulting from radiation therapy. A number of mouth rinse preparations exist for patients with treatment-related oral mucositis pain such as the DLA rinse, an over-the-counter medication. This study will evaluate the effects of doxepin compared to DLA (diphenhydramine, lidocaine and antacids) and placebo.Doxepin is approved by the Food and Drug Administration (FDA) for the treatment of depression, anxiety, long-term pain management, as well as management of rash.
详细描述
Patients are stratified according to sex (male vs. female), concurrent use of chemotherapy (no vs. yes), patient age at registration (< 60 years old vs. ≥ 60 years old and RTOG acute radiation morbidity criteria (1 vs. 2 vs 3 or more). Protocol therapy will consist of 2 cycles. Patients are randomized to one of three treatment regimens, which include doxepin, DLA and placebo. Cycle One will consist of one day. The care provider or nurse will confirm that the oral pain is at least 4 out of 10 severity level at the time of the rinse on the first day of the study. Patient will be asked to complete the baseline evaluation in the Oral Symptoms booklet. If the pain score is less than 4 then administration will be delayed until the pain is at least 4. Cycle Two will consist of an optional continuation phase lasting up to 7 days. Initiation of the Cycle 2/Continuation Phase may be delayed up to one week after Cycle 1/Day 1.
Primary Objective:
- Determine whether the doxepin rinse or DLA rinse is more effective than placebo in reducing OM-related pain in patients undergoing RT to the oral cavity, as measured by a patient-reported questionnaire at baseline, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, and 4 hours.
Secondary Objectives:
- Assess the adverse event profile of the doxepin rinse, the DLA rinse agent, and the placebo using a patient-reported questionnaire at 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, and 4 hours for domains of unpleasant taste, burning or stinging discomfort, and drowsiness.
- Compare the incidence of using additional analgesics between 1 and 4 hours after the initial mouthwash, between the doxepin oral rinse, the DLA rinse agent, and the placebo arms.
- Compare the length of time that each study product is used by patients in the one-week continuation phase.
- Compare the daily pain scores in the one-week continuation phase for the three study arms.
- Compare the 24-hour morphine equivalent dose used in the continuation phase for the three study arms.
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 (Participant, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
doxepin rinse
Patients receive 2.5 mL (25 mg) doxepin and 2.5 mL water orally. Doxepin rinse is administered in the clinic on Day 1 (Cycle 1). There is an optional continuation phase within seven days following Day 1 (Cycle 1), patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2) where the patient takes the rinse at home every 4 hours. Chemotherapy is allowed during the continuation phase. Patients randomized to doxepin or placebo, they and their caregivers will continue to be blinded to the treatment.
Patients will complete the Oral Symptoms booklet per the protocol.
干预措施: doxepin hydrochloride oral solution (Drug)
DLA (diphenhydramine, lidocaine and antacid) rinse
Patients receive 5.0 mL DLA orally. DLA is administered in the clinic on Day 1 (Cycle 1). There is an optional continuation phase within seven days following Day 1 (Cycle 1), patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2) where the patient takes the rinse at home every 4 hours. Chemotherapy is allowed during the continuation phase. Patients receiving DLA during the continuation phase of the study, they and/or caregivers may be aware that they are receiving DLA.
Patients will complete the Oral Symptoms booklet per the protocol.
干预措施: DLA (diphenhydramine, lidocaine and antacids) rinse (Drug)
placebo rinse
Patients receive 2.5 mL placebo and 2.5 mL water orally. The placebo rinse is administered in the clinic on Day 1 (Cycle 1). There is an optional continuation phase within seven days following Day 1 (Cycle 1), patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2) where the patient takes the rinse at home every 4 hours. Chemotherapy is allowed during the continuation phase. Patients randomized to doxepin or placebo, they and their caregivers will continue to be blinded to the treatment.
Patients will complete the Oral Symptoms booklet per the protocol.
干预措施: Placebo (Other)
结局指标
主要结局
Mean Area Under the Curve (AUC) of Total Pain Reduction
时间窗: Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment
Total pain reduction (mouth and throat) was measured by the numerical analogue scale of mouth pain on a scale of 0 to 10, with 0=no pain and 10=worst pain in the questionnaires taken at baseline, and 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total pain reduction was calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale (baseline, 5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 0, 1, 2, 3, 4, 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing baseline data, or only provided baseline data, he/she was excluded from the statistical analysis.
次要结局
- Area Under the Curve (AUC) of Total Unpleasant Taste of the Oral Rinse(5, 15, 30, 60, 120, 240 minutes post treatment)
- Area Under the Curve (AUC) of Total Stinging or Burning From the Oral Rinse(5, 15, 30, 60, 120, 240 minutes post treatment)
- Area Under the Curve (AUC) of Total Drowsiness(Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment)
- The Incidence of Using Alternative Analgesics(At 120 and 240 minutes post treatment)
- Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase(At 240 minutes post treatment)
- Frequency of Study Rinse Used in the Continuation Phase(Up to 7 days.)
- Median Mouth Pain Score in the Continuation Phase(Day 1 to Day 7 in the Continuation Phase)
- The Incidence of Using Alternative Analgesics in the Continuation Phase(Day 1 to Day 7 in the Continuation Phase)