Clinical trial NCT02309346: Clindamycin Once a Day in Septic Abortion
Official title: A Randomized Clinical Trial Between Clindamycin Once and Thrice a Day in Septic Abortion.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Septic Abortion
Keywords: clindamycin
septic abortion
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2014-12-05
Enrollment: 190
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Septic abortion is a serious condition. Women with septic abortion are treated with clindamycin plus gentamicin using divided doses, i.e., thrice a day.

The objective of this study is to compare the rates of cure between once or thrice a day use of clindamycin with gentamicin in cases of septic abortion.

Detailed description: Obstetric infections are very common, especially in developing countries, as a consequence of the practice of unsafe abortion. In these countries, an estimated five million women each year are hospitalized due to complications from induced abortions, which equates to a rate of 5-7 per thousand women.

Abortion remains a leading cause of maternal death in developing countries. According to the World Health Organization, it is estimated that 1 in 8 maternal deaths occur from complications of illegal abortion. Septic abortions play an important role in the maternal morbidity and mortality. The diagnosis of septic abortion should be considered when a woman of reproductive age presents with menstrual delay, vaginal bleeding accompanied by abdominal pain and fever.

In 1989, Plaisance et al. demonstrated that Clindamycin, an antibiotic used for septic abortion, could be prescribed at a dose of 12/12 hours, and bacterial inhibitory serum levels were similar to those in divided doses 6/6 hours. In 2003, Livingston et al. published the results of gentamicin and clindamycin combined in a single daily dose for cases of post-cesarean endometritis. Administration of clindamycin differed by being in a dose of 2700mg daily dose of different fractional 6/6 hours, or 8/8 hours, and the cure rates were 82% (45 of 56 cases successes) in a single daily dose (13). The etiology of postpartum endometritis is similar to that in infected abortion (14, 15), but little information exists regarding the use of single daily dose in this disease.

A retrospective study recently conducted by our group showed that patients with infected abortion treated with Clindamycin single dose achieved cure rates of 98% (95% CI - 95 to 99%), suggesting an equivalence between a single daily dose and treatment conventional three daily doses.

OBJECTIVES The objective of this study is to verify the equivalence of using Clindamycin once a day versus 3 times daily in the rates of cure of septic abortion.

Hypotheses H0: Ps\> Pn+2 The percentage of clinical cure with standard treatment (Ps) is greater than the rate of cure of alternative treatment + 2%.

Ha: Ps - 2% ≤ Pn The percentage of clinical cure with traditional treatment (Ps) minus 2% is less than or equal to the percentage of cure alternative treatment (Pn).

Variables

1. Standard treatment (Clindamycin 3x daily)
2. Alternative treatment (1x daily Clindamycin)
3. Clinical improvement (present or absent), defined as absence of fever (≤37.7 ° C), normal WBC (≤12.000 total leukocytes), eating and walking without difficulty, as already described in the literature.

Materials and methods Design Randomized, prospective, double-blind study with two arms that follow the parameters of the CONSORT (17).

Geographic and temporal limitations The study will be conducted in patients attending the emergency unit at HCPA. A period of 24 months for data collection (about 4 patients per month), it will be necessary to reach sample size.

Inclusion criteria

All patients who come to emergency unit at HCPA with clinical diagnosis of septic abortion and will be treated with Clindamycin will be invited. The diagnosis of infected abortion is the same as used previously described by our group (9). Briefly, the presence of one of the criteria below in a \< 20 weeks gestation, associated with a suspected ovular infection:

1. History of intrauterine manipulation with contaminated objects.
2. Vaginal discharge with foul odor.
3. Presence of pus flowing through the cervix.
4. Signs of peritoneal irritation.
5. leukocytosis (\> 14,000 leukocytes / ml).
6. Warm Extremities, thready pulse and tachycardia (HR\> 110 bpm)
7. Cyanosis and / or paleness
8. Tachypnea (MR\> 30mrpm)
9. hypotension (Systolic Blood Pressure \<90 mmHg)
10. Oliguria
11. Hyperthermia (≥ 37.8 ° C) Exclusion criteria

Will be excluded all patients who:

1. Do not wish to participate in the project.
2. They used antibiotics prior to hospitalization (1 week period).
3. Being allergic to clindamycin or gentamicin. Execution Patients eligible for the study will be invited to participate in the study at hospital admission for uterine curettage. After reading and signing the informed consent, patients will answer a standardized interview and after the interview, she will be randomized.

Randomization Subjects will be randomly allocated to treatment with clindamycin 3 times a day, or once a day; random sequence will be generated by a computer grouped into blocks of 4 treatments. The randomization sequence will be obtained from sequential sealed envelope that will be in possession of the pharmacy emergency service HCPA. Researcher will not have access to the following treatment sequence. The Pharmacy Service will prepare the medication that will be part of routine emergency Gynecological Unit.

Patients and researchers will be blind to treatment allocation; saline infusion will be given in the place of clindamycin to keep patients blind to treatment arm.

Treatment

The regimen will consist of:

Standard treatment (Ps.): Clindamycin (900mg intravenously 8/8 hours diluted in 250 ml saline 0.9% solution (SF). The first vial of SF will contain 240 mg of gentamicin.

Alternative treatment (Pn): Clindamycin (2700mg) + gentamicin (240 mg) diluted in 250 ml of 0.9% saline. Two additional vials of SF 0.9% will be infused every 8 h as placebo.

The treatment will be continued up to 48 hours of good clinical condition, defined as absence of fever, decreased vaginal bleeding, minimal or no pain (AVS \<4), leukocyte count within the normal range, evacuating and walking normally.

Follow-up All women included in the study will be reviewed within 7 days after discharge as routine at the gynecologic emergency unit, to receive the results of the pathology.

Outcomes

The following outcomes will be assessed:

1. Clinical improvement until discharge in number of days of hospitalization, complications related to treatment.
2. Treatment failure will be considered as persistence of fever (≥37.8ºC) during hospital admission, worsening of abdominal pain, persistent vaginal bleeding, need for exchange clindamycin due to treatment failure, or the need to add other antibiotics, either intravenously or orally.
3. Hospital readmission within 7 days after discharge due to fever (Tax ≥37.8ºC), persistent pelvic pain, persistence or increase of uterine bleeding, or other hospital admission related to the septic abortion.
4. Presence of urinary tract infection or candidiasis, persistence of ovular contents will not be considered as treatment failure.

Sample Size The sample size was calculated as a trial of non-inferiority, using the formula proposed in the literature (18). According to data obtained in a retrospective study by our group (16) we expect that the estimated rate of clinical cure is 99% (95% CI - 95 to 99%) in the group with three daily doses and 100% (95% CI - 99 to 100%) in the experimental treatment. For a non-inferiority study, using a power of 90%, an alpha error of 5% and a lower limit for non-inferiority of 2%, 95 cases will be needed in each group.

Statistical analysis Data will be analyzed by intention to treat and per protocol. The definition of intention to treat is based on the criteria suggested in the literature. The statistical analysis will be performed using Student t-test to compare the difference of means; chi-square test will be used to compare proportions with confidence intervals.

Eligibility criteria: Inclusion Criteria:

* Women with clinical diagnosis of septic abortion

Exclusion Criteria:

* Refuse to participate in the study
* Use of antibiotics with 1 week prior randomization
* Known allergy to clindamycin or gentamcin

Primary outcomes:
measure: Cure (Clinical improvement defined as reduce of pain, bleeding and no fever for 48h)
timeFrame: 72 hours
Secondary outcomes:
measure: Complications (Return to the hospital for admission related to the evacuation procedure within 7 days)
timeFrame: 7 days
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
Study officials:
affiliation: Federal University of Rio Grande do Sul
name: Ricardo F Savaris, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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