Rapidity of Response to Adalimumab Treatment in Patients With Crohn´s Disease (RAPIDA)

February 2, 2018 updated by: AbbVie

Rapidity of Onset of Response to Adalimumab in Luminal Crohn's Disease (RAPIDA Study)

The purpose of this study is to evaluate the rapidity of onset of clinical response to adalimumab therapy in patients with luminal Crohn's disease.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Crohn's disease (CD) diagnosed within, at least, the previous 4 months.
  • Patients with active luminal (Harvey-Bradshaw Index [HBI] ≥ 8) moderate to- severe CD.
  • No response to a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant.
  • If receiving any of the following treatments, their dose should be stable during the periods indicated:

    • Aminosalicylates for, at least, the last 4 weeks
    • Probiotics for, at least, the last 4 weeks
    • Analgesics for, at least, the last 4 weeks
    • Antidiarrheals for, at least, the last 4 weeks
    • CD-related antibiotics for, at least, the last 4 weeks
    • Azathioprine, 6-mercaptopurine or methotrexate for, at least, the last 12 weeks
  • If receiving any of the following treatments, their dose should not have been increase in the past two weeks (the dose reduction is permitted):

    • Oral budesonide (maximum dose of 9 mg/day)
    • Oral prednisone or equivalent (maximum dose of 40mg/day)

Exclusion Criteria:

  • Previous treatment with any anti-Tumor Necrosis Factor agent
  • Surgical bowel resection within the previous 6 months, ostomy, extensive bowel resection (> 100 cm), short bowel syndrome
  • Fistulising Crohn's disease
  • Treatment with cyclosporine or tacrolimus within the previous 8 weeks
  • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from screening, congestive heart failure of worse than grade II New York criteria (New York Heart Association Functional Classification).
  • Subject with an ostomy or ileoanal pouch, proctocolectomy, total colectomy, ileostomy, stoma or ileal pouch-anal anastomosis (Subjects with a previous ileo-rectal anastomosis are not excluded).
  • Screening laboratory values (according to central laboratory)
  • Known hepatitis C (HC) infection.
  • Serologic evidence of hepatitis B (HB) infection based on the results of testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs) antibodies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Adalimumab
Participants received adalimumab for 12 weeks (160 mg at Week 0; 80 mg at week 2; then adalimumab 40 mg every other week starting at Week 4).
Adalimumab pre-filled syringe, administered by subcutaneous injection
Other Names:
  • Humira, ABT-D2E7

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Clinical Response at Day 4
Time Frame: Day 4
Clinical response defined as a decrease of at least 3 points in Harvey-Bradshaw Index (HBI) score. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease.
Day 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Clinical Response at Week 1
Time Frame: Week 1
Clinical response defined as a decrease of at least 3 points in HBI score. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease.
Week 1
Percentage of Participants With Clinical Remission at Weeks 2 and 4
Time Frame: Weeks 2 and 4
Clinical remission defined as HBI < 5. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease.
Weeks 2 and 4
European Quality of Life (EuroQol) 5 Dimensions 3 Levels Questionnaire (EQ-5D-3L) Index Score: Change From Baseline to Week 12
Time Frame: Baseline (Week 0) and Week 12

The EQ-5D-3L is a standardized instrument for use as a measure of health-related quality of life (HRQoL) and consists of 2 components:

  1. The EQ-5D-3L Index Score has five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with 3 levels of severity for each dimension ('no problems', 'some problems', and 'extreme problems'). The level of severity reported on each of the EQ-5D-3L dimensions determines a unique health state. Health states are converted into a weighted health state index. These weights lie on a scale on which full health has a value of 1 and dead has a value of 0.
  2. The EQ-5D visual analog scale (VAS) is a 20-cm scale with endpoints labeled "best imaginable health" and "worst imaginable health" anchored at 100 and 0, respectively.

A positive change represents an improvement in HRQoL. Mean Baseline and mean change from Baseline to Week 12 in the EQ-5D-3L Index Score are presented.

Baseline (Week 0) and Week 12
European Quality of Life (EuroQol) 5 Dimensions 3 Levels Questionnaire (EQ-5D-3L) Visual Analog Scale (VAS): Change From Baseline to Week 12
Time Frame: Baseline (Week 0) and Week 12

The EQ-5D-3L is a standardized instrument for use as a measure of HRQoL and consists of 2 components:

  1. The EQ-5D-3L Index Score has five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with 3 levels of severity for each dimension ('no problems', 'some problems', and 'extreme problems'). The level of severity reported on each of the EQ-5D-3L dimensions determines a unique health state. Health states are converted into a weighted health state index. These weights lie on a scale on which full health has a value of 1 and dead has a value of 0.
  2. The EQ-5D VAS is a 20-cm scale with endpoints labeled "best imaginable health" and "worst imaginable health" anchored at 100 and 0, respectively.

A positive change represents an improvement in HRQoL. Mean Baseline and mean change from Baseline to Week 12 in the EQ-5D-3L VAS are presented.

Baseline (Week 0) and Week 12
Inflammatory Bowel Disease Quality-36 (IBDQ-36) Questionnaire Overall Score: Change From Baseline to Week 12
Time Frame: Baseline (Week 0) and Week 12
The IBDQ-36 is used to assess the HRQoL related to bowel symptoms. The IBDQ-36 overall score is calculated as the sum of thirty-six items, each scored on a 1 to 7 likert point scale, and ranges from 7 to 252. The highest score indicates the best HRQoL related to bowel symptoms. A positive change in IBDQ-36 overall score indicates an improvement in HRQoL due to inflammatory bowel disease. Mean Baseline and mean change from Baseline to Week 12 in the EQ-5D-3L VAS are presented.
Baseline (Week 0) and Week 12
Fatigue Impact Scale for Daily Use (D-FIS): Change From Baseline to Week 12
Time Frame: Baseline (Week 0) and Week 12
The D-FIS is used to measure the impact of fatigue on the daily lives of persons. The D-FIS overall score was calculated as the sum of eight items, each scored on a 0 to 4 point scale, and ranges from 0 to 32. A higher score indicates a higher impact of fatigue on daily life. A negative change in D-FIS Overall Score means an improvement in HRQoL due to fatigue. Mean Baseline and mean change from Baseline to Week 12 are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Hemoglobin
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, and coagulation (activated partial thromboplastin time [aPTT], international normalized ratio [INR], and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Hematocrit
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Erythrocytes
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Sedimentation Rate (ESR)
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: C-reactive Protein (CRP)
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Fecal Calprotectin
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Activated Partial Thromboplastin Time (aPTT)
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: International Normalized Ratio (INR)
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Fibrinogen
Time Frame: Baseline (Week 0) and Week 12
Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Baseline (Week 0) and Week 12
Percentage of Participants With Clinical Response at Day 4 or Week 12 and Clinical Remission at Week 12
Time Frame: Up to Week 12
The percentage of participants with clinical response (defined as decrease of at least 3 points in HBI score) at Day 4 or Week 1 and clinical remission (defined as a HBI < 5) at Week 12.
Up to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Ignacio Marín, PhD, Hospital General Universitario Gregorio Marañon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2014

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

May 23, 2014

First Submitted That Met QC Criteria

May 23, 2014

First Posted (Estimate)

May 28, 2014

Study Record Updates

Last Update Posted (Actual)

March 1, 2018

Last Update Submitted That Met QC Criteria

February 2, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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