Contact information
Type
Scientific
Primary contact
Prof Ricardo Savaris
ORCID ID
Contact details
Rua Ramiro Barcelos
2350/1125
Porto Alegre
90035-003
Brazil
rsavaris@hcpa.ufrgs.br
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
03-006
Study information
Scientific title
Acronym
DAZ
Study hypothesis
1 g of azithromycin once a week for two weeks is equivalent to 14 days of 200 mg doxycycline per day.
Ethics approval
Hospital de Clinicas de Porto Alegre (HCPA) Institutional Review Board (ref: IRB0000921)
Study design
Randomized double-blinded placebo trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Pelvic inflammatory disease
Intervention
Eligible patients were invited to participate in the doxycycline azithromycin protocol (DAZ). After giving written consent, a standardized interview, examination and specimen collection techniques were taken. Only three researchers will perform the physical exams. Whenever possible, the researcher that performed the first clinical examination on the first visit also did follow up on that patient.
A standardized screening examination, including a visual pain scale (0-10), and the McCormick modified pain scale was performed in the same sequence by the three researchers. A complete blood count, endometrial biopsy, urinalysis, and erythrocyte sedimentation rate will be performed on the first visit.
Endometrial samples will be divided into two equal amounts. One will be snap frozen in liquid nitrogen for Polymerase Chain Reaction (PCR) analysis and the other will be fixed in formaldehyde for histological analysis.
After the initial interview, the patient will receive a parenteral 250 mg ceftriaxone injection and will be randomly allocated to one of two treatment groups.
Randomization and treatment:
A restricted randomization sequence list was generated by computer, and was kept concealed from the researcher until the moment of assignment. We will consider subjects in blocks of four at a time to create the allocation sequence. After the patient is enrolled in the protocol, she will be blindly assigned to a coded treatment, either 14 days doxycycline or 1 g of azithromycin per week for two weeks. To avoid bias, the medication will be manipulated by the hospital pharmacy and will be put in identically coded blisters (treatment A, treatment B). To confirm compliance, a treatment of just seven days will be given to the patient, forcing her to return in seven days to receive the rest of the treatment. Because of the difference in the amount of capsules in each treatment, the azithromycin blister was filled up with placebo.
In the first visit, the patient will receive 250 mg intramuscular ceftriaxone and a blister for seven days treatment. The first dose of the medication (1 g of azythromycin, or 200 mg of doxycycline) will be taken in front of the physician. She will receive a leaflet and instructions of how she should take the rest of the medication. Special attention was taken about warning against taking the medication on an empty stomach, using analgesics, and abstaining from sexual intercourse until the treatment was completed. All women will be advised to have their partner treated with 1 g of azithromycin.
Endometrial biopsy and definition of endometritis:
The endometrial biopsy was performed at the office using a Karman plastic curette (MedGyn Products Inc., Lombard, IL, USA). Histopathological endometritis was defined by the presence of ≥1 plasma cell per X120 field in the endometrial stroma plus ≥5 neutrophils per X400 field in the endometrial surface.
PCR techniques will be used to investigate the presence of Neisseria gonorrhea and Chlamydia trachomatis in the endometrial samples.
Follow-up and adherence:
Participants will be monitored with in-person visits at 2, 7, 14 and 30 days. In each visit, the gynecological examination and the assessment of the pain will be registered. On day 7, the patient will return the first blister and receive the second one. Again, the first dose will be taken in front of the physician. On day 14, she will return the second blister. Adherence will be checked by absence of capsules in each blister. On day 30, another endometrial biopsy will be performed to measure histological cure and blood tests will be repeated.
Intervention type
Drug
Phase
Not Specified
Drug names
Ceftriane, azithromycin and doxycycline
Primary outcome measure
The primary outcome for the trial is clinical cure, defined as improvement or absence of the initial pain at day 14 compared to baseline.
Secondary outcome measures
1. A clinical cure, defined as 70% or greater reduction in the total tenderness score at day 14 compared to baseline
2. Histological cure defined as absence of plasma cell per X120 field in the endometrial stroma and <5 neutrophils per X400 field in the endometrial surface
3. Absence of Neisseria gonorrhea and Chlamydia trachomatis on endometrial samples on day 30 by PCR techniques
Overall trial start date
10/08/2003
Overall trial end date
10/05/2006
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. A history of pelvic discomfort for a period of 30 days or less
2. Findings of pelvic organ tenderness (uterine or adnexal) on bimanual examination
3. Leukorrhea and/or mucopurulent cervicitis and/or untreated known positive gonococcal or chlamydial cervicitis
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
112
Participant exclusion criteria
1. Current pregnancy as demonstrated by beta-Human Chorionic Gonadotrophin (HCG) or ultrasonography
2. Inability to tolerate an outpatient oral regimen as demonstrated by the vomiting of eight ounces of water one hour after taking 10 mg of metoclopramide
3. Presence of tubo-ovarian abscess, appendicitis or hemorrhagic ovarian cysts confirmed by ultrasound or laparoscopy
4. Pelvic pain over 30 days duration
5. Allergy to ceftriaxone, azithromycin or doxycycline
6. Antimicrobial therapy within seven days of recruitment
7. Delivery, abortion or gynecological surgery within 30 days
8. Prior hysterectomy or bilateral salpingectomy
9. Homelessness
10. Fever
11. Abdominal rebound tenderness
Recruitment start date
10/08/2003
Recruitment end date
10/05/2006
Locations
Countries of recruitment
Brazil
Trial participating centre
Rua Ramiro Barcelos, 2350/1125
Porto Alegre
90035-003
Brazil
Sponsor information
Organisation
Foundation for the Incentive of Research (Fundacao de Incentivo a Pesquisa) (FIPE) (Brazil)
Sponsor details
Rua Ramiro Barcelos 2350/2
Andar
Porto Alegre
90035-003
Brazil
l-cpesquisas@hcpa.ufrgs.br
Sponsor type
Charity
Website
http://www.hcpa.ufrgs.br/default.asp?sacao=Institucional&sPagina=96&gSysCodigoConexao=
Funders
Funder type
Charity
Funder name
Foundation for the Incentive of Research (Fundacao de Incentivo a Pesquisa) (FIPE) (Brazil)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
Results in: http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17601896
Publication citations
-
Results
Savaris RF, Teixeira LM, Torres TG, Edelweiss MI, Moncada J, Schachter J, Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial., Obstet Gynecol, 2007, 110, 1, 53-60, doi: 10.1097/01.AOG.0000268801.90261.27.