SubfertilityPhase 1/2NCT02865785
Effect of Intralipid Infusion in Patients With Recurrent Implantation Failure
A Phase 1/2 study testing Intralipid 20% in people with Subfertility, run by Ain Shams University at 1 site in Egypt.
Trial summary
The aim of present study is to evaluate the effect of intralipid 20% infusion, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test on clinical pregnancy rates in women with unexplained recurrent implantation failure. Read more about this study
- Who is it for?
- Ages 20 to 38 years, women only
- Conditions the study is for
- Subfertility
- What is being tested?
- Intralipid 20%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 320 participants
- Where
- 1 siteEgypt
- Study dates
- Jul 2016to Aug 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 38 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age 20-38 years of age.
- Recurrent implantation failure, defined as failure to achieve a recognizable intrauterine gestational sac by ultrasonography after transfer of at least four good-quality embryos in a minimum of three fresh or frozen IVF cycles (Coughlan et al, 2014).
- Good-quality embryos will be defined as those characterized by absence of multinucleated blastomeres, four or five blastomeres on day 2, seven or more cells on day 3, and ≤ 20% anucleated fragments (Van Royen et al, 1999).
- Normal transvaginal ultrasonography
- Normal office hysteroscopy.
- Normal hysterosalpingography.
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- Absence of any structural pathological findings in laparoscopy.
- Normal male and female karyotyping.
- Normal endocrinological profile during ovarian stimulation
- Normal anti-cardiolipin antibody IgG, IgM and lupus anticoagulant.
- Normal thrombophilia screen in the form of protein C, protein S, anti thrombin III, factor V mutations and factor V leiden.
- Elevated uterine natural killer cells (uNK) density in luteal phase endometrial biopsy, defined as ≥ 5% CD16+ CD56+ cells in the stroma underlying the luminal epithelium (Tang et al, 2013; Quenby et al, 2005).
- Normal parameters of male semen analysis according to WHO criteria 2010.
- Written and signed informed consent by the patient to participate in the study.
Who cannot join
- Age more than 38 years.
- Less than 3 failed IVF cycles.
- Poor embryo quality in previous IVF trials.
- Abnormal ultrasonographic finding, e.g. endometrial polyps, fibroids or ovarian cysts.
- Abnormal hysteroscopic finding, e.g. endometrial polyps, endometrial hyperplasia or fibroid.
- Abnormal hysterosalpingographic finding, e.g. hydrosalpinx or peritoneal adhesions.
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- Abnormal male or female karyotyping.
- Abnormal endocrinological profile during ovarian stimulation, e.g. hyperprolactinemia
- Expected poor ovarian responders according to Bologna criteria (Ferraretti et al, 2011), i.e. presence of at least two of the following three features:
- Presence of risk factor for poor ovarian response (POR) represented by advanced maternal age (≥ 40 years) or any other genetic or acquired conditions possibly linked to a reduced amount of resting follicles.
- A previous POR, represented by a cycle cancelled (following the development of less than three growing follicles) or the collection of less than four oocytes in response to an ovarian stimulation protocol of at least 150 IU FSH per day.
- An abnormal ovarian reserve test (i.e. AFC < 5-7 follicles or AMH < 0.5-1.1 ng/ml).
- Positive anticardiolipin antibodies or lupus anticoagulant.
- Positive thrombophilia screen.
- Normal uterine natural killer cells (uNK) density in luteal phase endometrial biopsy, defined as < 5% CD16+ CD56+ cells in the stroma underlying the luminal epithelium (Tang et al, 2013; Quenby et al, 2005).
- Abnormal semen analysis parameters according to WHO criteria 2010.
- Any chronic medical disorder, e.g. hypertension, autoimmune disorders, … etc.
- Known allergy to any of the intralipid constituents.
- Mental condition rendering the patients unable to understand the nature, scope and possible consequences of the study.
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
AinShams Maternity Hospital
Cairo, Cairo Governorate, 002
Khaled Afifi, MBBCH, 01009981222, DrKhaledAfifi@hotmail.com
About this study
Official title: Effect of Intralipid Infusion in Patients With Recurrent Implantation Failure (A Randomized Controlled Trial)
The aim of present study is to evaluate the effect of intralipid 20% infusion, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test on clinical pregnancy rates in women with unexplained recurrent implantation failure.
Read the detailed description
The study will include 300 women with unexplained recurrent implantation failure undergoing IVF/ICSI cycle.
Randomization:
Patients fulfilling the inclusion criteria will be randomized to two groups.
Study Group:
This group will include 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group will receive intravenous infusion of intralipid 20%, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test.
Control Group:
This group will include 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group will receive intravenous infusion of placebo, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test.
Random allocation sequence generation:
A computer generated list via MedCalc ® Software, version 13.2.2 will be used, assigning each participant number to either study groups.
Allocation Concealment:
Assignment will be done by sequentially numbered, otherwise identical, sealed envelopes (SNOSE), each containing a 2-inch by 2-inch paper with a written code designating the assigned group. These papers will be placed in a folded sheet of aluminum foil fitted inside the envelope. Effort will be taken to assure absence of any detectable differences in size or weight between intervention and control envelopes. Envelopes will be chosen to be opaque and lined inside with carbon paper. Envelopes will be opened sequentially only after writing the subject's tracking information on the envelope so that the carbon paper served as an audit trail.
Blinding:
Both drug with active ingredient and placebo will be provided by the hospital pharmacy in identical sealed opaque containers, equal in weight, similar in appearance, and tamper-proof. The drug with the active ingredient containers will be labeled either Group A or Group B by the head pharmacist and the assignment kept secret to be revealed after the end of the study.
Drugs will be administered to patients by a sealed opaque infusion drip.
An endometrial biopsy (Wallach endocell sampler ® ) will be taken during the luteal phase of the menstrual cycle and put in formalin. The biopsy will be embedded in paraffin, cut into sections and immunohistochemistry will be used to identify uNK cells using an antibody to CD56 and CD16 (NCL-CD56-16; Novacastra ® ). A cut-off of normality of 5% uNK cell density will be used.
IVF/ICSI cycle will be done using the standard LLP in both groups.
primary outcome will be Live birth rate.
secondary outcomes will be biochemical and clinical pregnancy rates.
- Conditions
- Subfertility
- Being tested
- Intralipid 20%, Placebo
- Keywords
- recurrent implantation failure, intralipid, uterine natural killer cells
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intralipid 20%Drug
Also called lipofundin 20%
intralipid D4-9 of induction ovulation to be repeated within 7 days of positive pregnancy test.
PlaceboDrug
Also called saline 0.9%
saline infusion D4-9 of induction of ovulation to be repeated within 7 days of positive pregnancy test.
| Study group | Role | What they receive |
|---|---|---|
| Study Group | Active comparator | This group will include 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group will receive intravenous infusion of intralipid 20% (100 mL of intralipid 20% diluted in 250 mL sterile i.v. saline administered i.v. over two hours), once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test. Receives: Drug: Intralipid 20% |
| Placebo Group | Placebo comparator | This group will include 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group will receive intravenous infusion of placebo, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate
Measured: 38 gestational weeks
Secondary outcomes (2)
Clinical pregnancy rate
Measured: 6 gestational weeks
Chemical pregnancy rate
Measured: 6 gestational weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2016 (estimated)
- Study startJul 2016
- Primary completionJul 2017 (estimated)
- Study completionAug 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SubfertilityStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mostafa Fouad Gomaa, Ain Shams University
- Investigators
- Khaled Afifi, MBBCH, Study director, Resident of O&G
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02865785
- Sponsor's protocol ID
- Intralipid-RIF
- Status last verified
- Aug 2016
- First submitted
- 10 Aug 2016
- Last updated
- 12 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Intralipid Infusion in Patients With Recurrent Implantation Failure (A Randomized Controlled Trial)
- ClinicalTrials.gov ID
- NCT02865785
- Acronym / sponsor ID
- Intralipid-RIF
- Conditions
- Subfertility
- Keywords
- recurrent implantation failure, intralipid, uterine natural killer cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- Jul 2016
- Primary completion
- Jul 2017 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 12 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of present study is to evaluate the effect of intralipid 20% infusion, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test on clinical pregnancy rates in women with unexplained recurrent implantation failure.
Detailed description
The study will include 300 women with unexplained recurrent implantation failure undergoing IVF/ICSI cycle.
Randomization:
Patients fulfilling the inclusion criteria will be randomized to two groups.
Study Group:
This group will include 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group will receive intravenous infusion of intralipid 20%, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test.
Control Group:
This group will include 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group will receive intravenous infusion of placebo, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test.
Random allocation sequence generation:
A computer generated list via MedCalc ® Software, version 13.2.2 will be used, assigning each participant number to either study groups.
Allocation Concealment:
Assignment will be done by sequentially numbered, otherwise identical, sealed envelopes (SNOSE), each containing a 2-inch by 2-inch paper with a written code designating the assigned group. These papers will be placed in a folded sheet of aluminum foil fitted inside the envelope. Effort will be taken to assure absence of any detectable differences in size or weight between intervention and control envelopes. Envelopes will be chosen to be opaque and lined inside with carbon paper. Envelopes will be opened sequentially only after writing the subject's tracking information on the envelope so that the carbon paper served as an audit trail.
Blinding:
Both drug with active ingredient and placebo will be provided by the hospital pharmacy in identical sealed opaque containers, equal in weight, similar in appearance, and tamper-proof. The drug with the active ingredient containers will be labeled either Group A or Group B by the head pharmacist and the assignment kept secret to be revealed after the end of the study.
Drugs will be administered to patients by a sealed opaque infusion drip.
An endometrial biopsy (Wallach endocell sampler ® ) will be taken during the luteal phase of the menstrual cycle and put in formalin. The biopsy will be embedded in paraffin, cut into sections and immunohistochemistry will be used to identify uNK cells using an antibody to CD56 and CD16 (NCL-CD56-16; Novacastra ® ). A cut-off of normality of 5% uNK cell density will be used.
IVF/ICSI cycle will be done using the standard LLP in both groups.
primary outcome will be Live birth rate.
secondary outcomes will be biochemical and clinical pregnancy rates.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Group | Active comparator | Drug: Intralipid 20%This group will include 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group will receive intravenous infusion of intralipid 20% (100 mL of intralipid 20% diluted in 250 mL sterile i.v. saline administered i.v. over two hours), once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test. |
| Placebo Group | Placebo comparator | Drug: PlaceboThis group will include 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group will receive intravenous infusion of placebo, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test. |
Who may qualify
- Ages
- 20 to 38 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Age 20-38 years of age.
- Recurrent implantation failure, defined as failure to achieve a recognizable intrauterine gestational sac by ultrasonography after transfer of at least four good-quality embryos in a minimum of three fresh or frozen IVF cycles (Coughlan et al, 2014).
- Good-quality embryos will be defined as those characterized by absence of multinucleated blastomeres, four or five blastomeres on day 2, seven or more cells on day 3, and ≤ 20% anucleated fragments (Van Royen et al, 1999).
- Normal transvaginal ultrasonography
- Normal office hysteroscopy.
Key exclusion criteria (19 listed)
- Age more than 38 years.
- Less than 3 failed IVF cycles.
- Poor embryo quality in previous IVF trials.
- Abnormal ultrasonographic finding, e.g. endometrial polyps, fibroids or ovarian cysts.
- Abnormal hysteroscopic finding, e.g. endometrial polyps, endometrial hyperplasia or fibroid.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intralipid 20%Also: lipofundin 20%intralipid D4-9 of induction ovulation to be repeated within 7 days of positive pregnancy test. | Drug | Study Group |
| PlaceboAlso: saline 0.9%saline infusion D4-9 of induction of ovulation to be repeated within 7 days of positive pregnancy test. | Drug | Placebo Group |
Primary outcome
Live birth rate
Time frame: 38 gestational weeks
2 secondary outcomes
Clinical pregnancy rate
Time frame: 6 gestational weeks
Chemical pregnancy rate
Time frame: 6 gestational weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Khaled Afifi, MBBCH study director
Resident of O&G
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Intralipid 20% in people with Subfertility, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Khaled Afifi, MBBCH (01009981222, DrKhaledAfifi@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth rate (time frame: 38 gestational weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2016.