The Use of Antibiotics After Hospital Discharge in Septic Abortion (APA)

A Randomized Clinical Trial on the Use or Not of Antibiotics After Hospital Discharge in Septic Abortion.

The use of antibiotics in post-partum infection has been abbreviated. After 48 hours of clinical improvement, the patient is discharged from the hospital without antibiotics. No trials has been found in cases of septic abortion.

The purpose of the present study is to verify the need of antibiotics after clinical improvement in cases of septic abortion.

Study Overview

• Status: Terminated
• Conditions: Abortion, Septic
• Intervention / Treatment: Drug: placebo; Drug: doxycycline plus metronidazole

Detailed Description

Septic abortion is still a major cause of maternal mortality in developing countries. According to the WHO, 1 woman dies for every 270 illegal abortion (Ahman E, 2004). Infected abortion has an important role in maternal morbidity and mortality (Stubblefield PG, 1994). the diagnosis of infected abortion must be considered when a patient presents a history of delayed menses, vaginal bleeding, abdominal pain and fever (Brasil, 2000)

Prompt diagnosis and treatment are paramount steps to prevent complications. At Hospital de Clínicas de Porto Alegre, the use of gentamycin plus clindamicin before curettage is preconized (Savaris R, 2006). Nevertheless, the time of treatment it is not well established, varying from 7-14 days (Brasil, 2000).

A recent study with post-partum endometritis has shown that it is not necessary to extend the treatment to 14 days, after clinical improvement (Turnquest MA, 1998; French LM, 2004)

A randomized clinical trial comparing placebo with the standard protocol of treatment would define weather both treatments are equivalent or not.

Comparison: The prolonged use of antibiotics, after intravenous use of antibiotics and clinical improvement, will be compared to the use of placebo in cases of septic abortion.

Sample size and ethical issues The study protocol was approved by the ethics committee of Hospital de Clínicas de Porto Alegre.

To compare equivalence between the 2 treatments we calculated the sample size considering an alpha error of 0.05, a beta error of 0.1, and difference between the two groups of no more than 10%. We expected a 99% clinical cure with the standard protocol, and 95% for the alternative one. These figures yield a minimum of 42 patients in each group. Interim analysis will performed at 58 for possible early stopping, if clinical cure was < 95%, or for sample size re-estimation.

Randomization and treatment Subjects will be allocated in blocks of four at a time to create the allocation sequence. If the patient was eligible for the study, she will be allocated to one of the 2 treatments. The allocation will be concealed, coded and obtained from a central telephone number. Patients and those who assessed the outcomes were blind to group assignment. To avoid bias, both medications were manipulated by the hospital pharmacy and put in identically coded blisters and capsules.

Statistical analysis Student´s t-test, Mann-Whitney test, and Fisher´s exact test will be used for statistical analysis. The rates of cure were analyzed by "modified" intention to treat (Keech AC, 2003) and per protocol with 95% confidence intervals.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
      • Hospital de Clínias de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients admitted at the hospital with a diagnosis of infected abortion and about to be discharged from the hospital.
• Use of intravenous antibiotics (gentamicin and clindamycin)
• Improvement of the clinical conditions for at least 48 hours (no fever, eating and walking normally, reduced vaginal bleeding)

Exclusion Criteria:

• Unwilling to participate in the study.
• Use of antibiotics previously within one week.
• Presence of tubo-ovarian abscess.
• Known allergy to doxycycline or metronidazole.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Patients that receive up to 10 days of doxycycline 200mg/day and metronidazole 500mg/day	Drug: doxycycline plus metronidazole; doxycycline 200mg/day plus metronidazole 500mg/day up to 10 days of treatment (additional to the hospital treatment); Other Names: Flagyl; Vibramicina
Placebo Comparator: 2; Patients that do not receive antibiotics, only placebo	Drug: placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical cure defined as no fever, no abdominal pain or bleeding.	10 days after hospital discharge

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Ricardo F Savaris, MD, PhD, Hospital de Clínicas de Porto Alegre

Publications and helpful links

General Publications

• Stubblefield PG, Grimes DA. Septic abortion. N Engl J Med. 1994 Aug 4;331(5):310-4. doi: 10.1056/NEJM199408043310507.
• Turnquest MA, How HY, Cook CR, O'Rourke TP, Cureton AC, Spinnato JA, Brown HL. Chorioamnionitis: is continuation of antibiotic therapy necessary after cesarean section? Am J Obstet Gynecol. 1998 Nov;179(5):1261-6. doi: 10.1016/s0002-9378(98)70143-7.
• French LM, Smaill FM. Antibiotic regimens for endometritis after delivery. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001067. doi: 10.1002/14651858.CD001067.pub2.
• Heritier SR, Gebski VJ, Keech AC. Inclusion of patients in clinical trial analysis: the intention-to-treat principle. Med J Aust. 2003 Oct 20;179(8):438-40. doi: 10.5694/j.1326-5377.2003.tb05627.x. No abstract available.
• Ahman E, Shah I. Unsafe abortion: worldwide estimates for 2000. Reprod Health Matters. 2002 May;10(19):13-7. doi: 10.1016/s0968-8080(02)00012-5.
• Brasil.Ministério da Saúde. Abortamento infectado. In: Ministério da Saúde, ed. Urgências e emergências maternas: guia para diagnóstico e conduta em situações de risco de morte materna. 1 ed. Brasília: MS/FEBRASGO; 2000: 13-17.
• Savaris R. Abortamento. In: Freitas FM, Costa SMH, Lopes JG, eds. Rotinas em Obstetrícia. 5 ed. Porto Alegre: Artmed; 2006: 70-77.

Helpful Links

• location of the study

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: July 13, 2006
• First Submitted That Met QC Criteria: July 17, 2006
• First Posted (Estimate): July 19, 2006

Study Record Updates

• Last Update Posted (Estimate): December 19, 2008
• Last Update Submitted That Met QC Criteria: December 18, 2008
• Last Verified: March 1, 2007

More Information

Terms related to this study

• Keywords: placebo; metronidazole; doxycycline; treatment period; infected abortion
• Additional Relevant MeSH Terms: Infections; Pregnancy Complications; Abortion, Spontaneous; Pregnancy Complications, Infectious; Abortion, Septic; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Metronidazole; Doxycycline
• Other Study ID Numbers: 05-452; GPPG 05-452