Use of G-CSF for the Treatment of Unexplained Recurrent Miscarriage

NCT ID: NCT00772122

Last Updated: 2008-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-01-31
• Study Completion Date: 2007-01-31

Brief Summary

In order to investigate the effectiveness of G-CSF in preventing embryo demise, the investigators administered this cytokine to women with recurrent miscarriage in a randomized controlled study compared to women treated with placebo. Sixty eight women with unexplained primary recurrent miscarriage, all of them with at least four consecutive abortions and negative for all clinical investigations were selected for this study. Patients were randomly treated with G-CSF, starting on the 6th day after ovulation, or with placebo.

Detailed Description

The patients with unexplained primary (no previous successful pregnancy) recurrent miscarriage (RM) referred to the Hungaria Center for Endocrinology and Reproductive Medicine between January 2000 to January 2007 were considered eligible for the study. The patients had to fulfil the following inclusion criteria: woman's age less than 39 years, more than 4 previous abortions, failure of a previous treatment for RM (immunoglobulin infusion), and they had to be negative for the all the known causes of RM The study was reviewed and approved by the Institutional Review Board, and the clinical study was conducted according to Italian law and the Declaration of Helsinki for Medical Research involving Human Subjects. A sample size calculation showed that a total of 32 patient per group were needed in order to have a difference of 33% between the two groups a for p<0.005 and a beta>0.80 A total of 72 patients were considered eligible for the study, and 68 of them agreed to participate, signing an informed consent form. All the patients were informed about the eventual potential risks of this treatment for the mother and the foetus, other than the lack of information about the developmental toxicity of G-CSF. The patients were randomized by means of a computer generated randomization number sequence. All the patients were informed about the therapy and they gave their written informed consent. They were randomly assigned to the two arms of the study, one to G-CSF treatment and the other to placebo administration; the patients were blind to which treatment they were assigned to. The G-CSF group of 35 women, underwent a daily sub-cutaneous administration of the filgrastim (Neupogen, Dompe', Italy), the recombinant G-CSF, at a dosage of 1 microgram (100000 IU)/kg/day from the 6th day after ovulation till the occurrence of menstruation or to the end of the 9th week of gestation. The placebo group consisting of 33 subjects, was given a treatment with subcutaneous saline solution at the dosage of 0.2 ml daily, and also in this case, from the 6th day after the ovulation till to the recurrence of menstrual loss or to the end of the 9th week. Primary outcome was considered the pregnancy outcome.

Conditions

Habitual Abortion

Keywords

Recurrent Miscarriage; G-CSF; pregnancy outcome; pregnancy outcome of pregnancies treated with G-CSF; treatment of recurrent miscarriage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Granulocyte colony stimulating factor

The G-CSF group of 35 women, underwent a daily sub-cutaneous administration of the filgrastim (Neupogen, Dompe', Italy), the recombinant G-CSF, at a dosage of 1 micro gram (100000 IU)/kg/day from the 6th day after ovulation till the occurrence of menstruation or to the end of the 9th week of gestation.

Group Type: EXPERIMENTAL

G-CSF

Intervention Type: DRUG

daily sub-cutaneous administration of the recombinant G-CSF, at a dosage of 1 microgram (100000 IU)/kg/day from the 6th day after ovulation till the occurrence of menstruation or to the end of the 9th week of gestation.

placebo (saline solution)

The placebo group consisting of 33 subjects, was given a treatment with saline solution at the 0.2ml/day subcutaneously/, from the 6th day after the ovulation till to the recurrence of menstrual loss or to the end of the 9th week.

Group Type: PLACEBO_COMPARATOR

saline solution

Intervention Type: DRUG

daily sub-cutaneous administration of saline solution 0.2ml from the 6th day after the ovulation till to the recurrence of menstrual loss or to the end of the 9th week.

Interventions

G-CSF

daily sub-cutaneous administration of the recombinant G-CSF, at a dosage of 1 microgram (100000 IU)/kg/day from the 6th day after ovulation till the occurrence of menstruation or to the end of the 9th week of gestation.

Intervention Type: DRUG

saline solution

daily sub-cutaneous administration of saline solution 0.2ml from the 6th day after the ovulation till to the recurrence of menstrual loss or to the end of the 9th week.

Intervention Type: DRUG

Other Intervention Names

filgrastim (Neupogen, Dompe', Italy),

Eligibility Criteria

Inclusion Criteria

• four or more previous consecutive abortion,
• failed previous treatment with intravenous immunoglobulins
• negative to all clinical investigation for recurrent miscarriage

Exclusion Criteria

• in the last abortion a fetal karyotype showing chromosomal abnormality
• previous successful pregnancy

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Florence

OTHER

Sponsor Role: lead

Responsible Party

CERM

Principal Investigators

Fabio Scarpellini, MD

Role: PRINCIPAL_INVESTIGATOR

Centre for Endocrinology and Reproductive Medicine, Italy

Locations

CERM

Rome, , Italy

Countries

Italy

References

Scarpellini F, Sbracia M. Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomised controlled trial. Hum Reprod. 2009 Nov;24(11):2703-8. doi: 10.1093/humrep/dep240. Epub 2009 Jul 17.

Reference Type: DERIVED

PMID: 19617208 (View on PubMed)

Other Identifiers

CERM0103

Identifier Type: -

Identifier Source: org_study_id