Randomized Multicentric Trial to Evaluate a Free Diet With a Progressive Diet in the Treatment of Acute Diverticulitis (DIVERDIET)

Sponsor

Hospital General Universitario Reina Sofía de Murcia (Other)

Overall Status

Completed

CT.gov ID

NCT03496090

Collaborator

(none)

134

Enrollment

Location

Arms

Actual Duration (Months)

11.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase III trial is designed to demonstrate the non-inferiority of a free diet versus a progressive diet in the treatment of acute diverticulitis (AD) without complications. In this study, the effectiveness of the short-term free diet is evaluated, as well as its safety and the quality of life that is perceived in front of the progressive diet.

Condition or Disease	Intervention/Treatment	Phase
Diverticulitis Acute Diverticulitis Diverticulitis, Colonic Uncomplicated Diverticular Disease Diverticulitis of Sigmoid Diet Modification Dietary Modification	Other: Free diet Other: Progressive diet	N/A

Detailed Description

The study will be carried out in the General Surgery and Gastroenterology Services of the following centers:

Hospital General Universitario Reina Sofía
Hospital General Universitario Morales Meseguer de Murcia.
Hospital Universitario Santa Lucía de Cartagena.
Hospital General Universitario de Elche.
Complejo Hospitalario Torrecárdenas de Almería

All patients with increased temperature and acute abdominal pain, as well as clinical suspicion of AD, will be screened for their potential selection in the study. Basic blood tests (hemogram) and abdominal ultrasound will be performed and these guidelines will be followed: if the results indicate complicated AD, it will be excluded from the study; if uncomplicated DA is suspected, blood CRP will be requested; if CRP is less than 5 mg / dl, it will be included in the study and ambulatory treatment will be indicated; if CRP is greater than 5mg / dl, abdominal CT with intravenous contrast will be requested. Result: uncomplicated DA, it will be included in the study and it will be indicated ambulatory treatment or complicated DA, it will be excluded from the study-; those patients with uncomplicated AD, but with risk factors, hospital admission will be recommended, and they may be offered to participate in the study.

If the patient meets the criteria for admission to the study, the attending physician (surgeon on duty) will inform and invite them to participate and after signing the informed consent, their data will be collected and they will be contacted. the person of the hospital, in charge of guarding the list and randomization codes to assign him the corresponding research group: group 1 (free diet) or group 2 (progressive diet) (Annex III), - this group will be delivered of your printed diet and you will be instructed about it, as well as, to all patients, the annotations of pain control and temperature on ad-hoc sheet. The patient data will be delivered to the investigator / s of the study of each hospital, who will fill in the Data Collection Notebook (DCN) of each patient and program their controls without information of the group to which the patient has been assigned, as In this way, the consultations are carried out with blinding of the evaluator (the investigator who will do the controls will not know to which group the patient has been assigned). They will also be asked a quality of life questionnaire SF-12 (baseline) and they will be asked for a blood test with a complete blood count and CRP for the 3rd day of treatment.

Outpatients will be contacted daily by phone during the first 3 days of treatment by the study investigator and between the 3rd and 4th day will go to outpatient surgery for clinical and analytical control (1st consultation), filling in the DCN. The hospitalized patients will follow the same clinical and analytical control by the plant surgeon and the study investigator, filling in the DCN. They will be asked for new blood tests with CRP for the 7th day of treatment and, in those patients who do not have a colonoscopy in the last 12 months prior to entering the study, an endoscopic study will be requested before 60 days for confirmation of diverticular disease, filling in the DCN. They will be given a new SF-12 quality of life questionnaire that they will fill out on the 7th day of the start of the treatment. They will be cited for a new consultation (2nd consultation) to all patients (outpatients and those who have been hospitalized), 30 days of the beginning of the treatment, with new clinical control and annotation of the last analytical, as well as third and last SF-12 quality of life questionnaire, in the DCN. To conclude, patients who were asked for colonoscopy, will be cited in a final consultation (3rd) 2 months after beginning the treatment with the endoscopic result closing the study, with the last entries in the DCN.

Sample size:

To obtain a power of 80% to reject the null hypothesis Ho: that the difference of proportions p1 and p2 is lower than the non-inferiority limit of -10, and taking into account that the level of significance is 5%, assuming that the proportion of non-treatment failure in both treatment groups is 94.7%, the total number of patients expected to be included in the study is 134 patients, with an expected percentage of dropouts of 5%, which 67 patients will receive treatment through free diet and other 67 patients through progressive diet. The endpoint for the main comparison is the proportion of subjects with a lower treatment failure rate at one month (30 days) of follow-up.

Statistical treatment:

The continuous variables will be summarized using descriptive statistics: mean, standard deviation (SD), median, minimum, maximum, number of observations and number of missing observations. Non-normal continuous data will be presented as maximum, top quartile, median, lowest quartile, minimum and number of observations. The categorical variables will be described using absolute and relative frequencies.

For the comparisons between variables, the bivariate analysis will be used. The scores of each dependent variable will be compared with the independent variables using parametric statistical methods (and nonparametric when the parametric application criteria are not met). When the changes within the same treatment group are analyzed, statistical tests for related or paired samples will be used.

In the event that the variables follow the normal distribution, one or more of the following techniques will be described:

If a variable is of a quantitative type and the other is categorical, for the comparison of the means with a dichotomous variable, the Student's t test will be used. In cases where the qualitative variable has more than 2 categories, the one-way variance analysis (ANOVA) will be used. In the analysis of the variance of a factor with repeated measures, it will be assumed that the subjects are randomly selected from normal populations with the same variance. Previously, the assumptions of independence, normality and equality of variances will be checked.

In the case that the variables do not follow the normal distribution:

If one variable is quantitative and the other qualitative, the test to be applied will be the Mann-Whitney U test when the qualitative variable has 2 levels, and the Kruskall-Wallis test if the qualitative measurement is formed by 3 levels or plus.
If both variables are of the categorical type, a cross-tabulation will be performed (contingency tables) using the Pearson chi-square statistic to test the independence hypothesis or the Fisher test (in 2 x 2 tables) ). An analysis of typed residuals corrected will be carried out in order to interpret the meaning of the association detected.

For the non-inferiority analysis in the main variables, a calculation will be made using the Farrington-Manning score, Miettinen-Nurminen Score and Gart-Nam Score tests, with a significance level of 0.05, and a limit of no- inferiority of 0.10. For the continuous variables, non-inferiority will be evaluated by the difference of means with the Mann-Whitney U and the Wilcoxon test.

All statistical comparisons will be made using statistical tests with a level of significance p = 0.05.

Study Design

Study Type:

Interventional

Actual Enrollment :

134 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The study is a randomized, multicentric, controlled with active comparator, parallel group, blind to the evaluator, to demonstrate the non-inferiority in the efficacy and therapeutic and safety of the free diet (group 1) compared to the progressive diet (group 2) in the treatment of uncomplicated acute diverticulitis. This study will be carried out on 134 patients with uncomlpicated acute diverticulitis. The subjects will be randomized in a 1: 1 ratio to receive treatment with progressive diet or diet at free demand. The main analysis will take place two months after the start of treatment.The study is a randomized, multicentric, controlled with active comparator, parallel group, blind to the evaluator, to demonstrate the non-inferiority in the efficacy and therapeutic and safety of the free diet (group 1) compared to the progressive diet (group 2) in the treatment of uncomplicated acute diverticulitis. This study will be carried out on 134 patients with uncomlpicated acute diverticulitis. The subjects will be randomized in a 1: 1 ratio to receive treatment with progressive diet or diet at free demand. The main analysis will take place two months after the start of treatment.

Masking:

Double (Investigator, Outcomes Assessor)

Masking Description:

The patient data will be delivered to the investigator/s of the study of each hospital, who will fill out the Data Collection Notebook (DCN) of each patient and program their controls without information of the group to which the patient has been assigned, as such In this way, the consultations are carried out with blinding of the evaluator (the investigator who will do the controls will not know to which group the patient has been assigned). The person in charge of carrying out the statistical analysis will not be able to know to which group the patient has been assigned due to the coding done in the DCN.

Primary Purpose:

Treatment

Official Title:

Randomized Multicentric Controlled Clinical Trial of Parallel Groups to Evaluate the Non-therapeutic Inferiority of a Free Diet With a Progressive Diet, in the Treatment of Non-complicated Acute Diverticulitis

Actual Study Start Date :

Apr 16, 2018

Actual Primary Completion Date :

Jan 31, 2019

Actual Study Completion Date :

Apr 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Free diet Free diet or free demand, being comparable to the normal or zero hospital diet	Other: Free diet Free diet or free demand, being comparable to the normal or zero hospital diet Other Names: Basal diet
Active Comparator: Progressive diet Progressive diet for 7 days, liquid diet for the first three days and soft diet without waste, from the 4th to the 7th day.	Other: Progressive diet Progressive diet for 7 days, liquid diet for the first three days and soft diet without waste, from the 4th to the 7th day.

Arm

Intervention/Treatment

Experimental: Free diet

Free diet or free demand, being comparable to the normal or zero hospital diet

Other: Free diet

Free diet or free demand, being comparable to the normal or zero hospital diet

Other Names:

Basal diet

Active Comparator: Progressive diet

Progressive diet for 7 days, liquid diet for the first three days and soft diet without waste, from the 4th to the 7th day.

Other: Progressive diet

Progressive diet for 7 days, liquid diet for the first three days and soft diet without waste, from the 4th to the 7th day.

Outcome Measures

Primary Outcome Measures

Success in the treatment [30 days]
Absence of persistence, increase or recurrence of abdominal pain or fever, transition to a stage higher than that of the modified Hinchey classification (requiring radiological drainage and / or surgical treatment), need for hospital admission (for outpatients) and death attributed to this diagnosis.

Secondary Outcome Measures

Pain score [7 days]
The evaluation in each treatment group of pain intensity, using visual analogue scale (VAS) of pain, self-evaluated daily after dinner. Min value 0. Max value 10. Higher values represent a worse outcome.
Body temperature [7 days]
Axillary temperature curve, as a reference, by one shot every 12 hours.
PCR value [day 0, 3 and 7]
The comparison in each treatment group of the levels of C-reactive protein (CRP).
Increase in stage [30 days]
Percentage of patients in each treatment group who pass to a stage higher than Ia in the Hinchey classification modified.
Need for hospital admission [30 days]
Percentage of outpatients in each treatment group who require hospital admission.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of uncomplicated acute diverticulitis
Adequate oral tolerance
Good response to the first emergency treatment measures (analgesics and antibiotic therapy): improvement of pain and decrease in temperature.
Willing to continue treatment at home under supervision.
Accept sign informed consent.

Exclusion Criteria:

Acute complicated diverticulitis (from grade Ib of the modified Hinchey Classification).
No good response to the first emergency treatment measures (analgesics and antibiotics): maintenance or increase of abdominal pain, persistence of fever, oral intolerance or vomiting, clinical worsening.
Antibiotic treatment for diverticulitis in the previous month.
Suspicion of colorectal cancer.
Pregnant.
Refuses to sign informed consent.