The IMPACT Study: IMProve Pregnancy in APS with Certolizumab Therapy

Institutional Review Board, Hospital for Special Surgery

December 03, 2020

The safety of study participants is our top priority. The trial is approved and periodically reviewed by an Institutional Review Board (IRB), which includes doctors, administrators, ethicists, and members of the general public. The safety of clinical trials is reviewed by the U.S. Food and Drug Administration.

Before enrolling in a clinical trial, the investigator will explain the purpose of the trial, its expected benefits, any possible risks or side effects, and what your role will be. This is the time to ask questions! If you want to join the trial, you must sign the informed consent documents. You can leave a clinical trial at any time without penalty.

For further information, see Understanding Clinical Trials.

Principal Investigator

Jane E. Salmon, MD

Co-Investigators

Avi Mikhaylov
Margaret Minett​​​​​​​​​​​​​​
Hayley Slosberg
​​​​​​​

Summary

Patients with antiphospholipid syndrome are at increased risk for pregnancy complications, and inflammation contributes to injury of the placenta. Studies in animal models have shown that  blockade to TNF, a cytokine of inflammation, prevents pregnancy complications.  

The objective of this trial is to evaluate whether adding certolizumab to standard treatment will decrease the frequency of severe pregnancy complications, such as preeclampsia, in pregnant women with antiphospholipid syndrome (APS) and repeatedly positive tests for lupus anticoagulant (LAC).

All patients will receive certolizumab, a TNF blocking medication that does not cross the placenta, in addition to the heparin and aspirin prescribed by their physician. The medication will be injected subcutaneously by the participant every other week from eight weeks through 28 weeks of pregnancy.

Pregnancy outcomes will be compared to those of women with APS and repeatedly positive tests for LAC enrolled in a previous study by the investigators.

Inclusion/Exclusion Criteria

Inclusion Criteria:

• Pregnant as defined by positive test for elevated ß-HCG and having a live, appropriate sized embryo by ultrasound, but <8 weeks gestation;

• APS and positive for LAC on two or more occasions greater than 12 weeks apart within the previous 18 months and confirmed by review of medical records and core laboratory testing;

  a: The diagnosis of APS and LAC will be confirmed by one of the Co-PIs for each case by a review of the medical records.

• Age 18-38 (+364 days) years of age and able to give informed consent
• Laboratory hematocrit >26% at time of screening.

Exclusion Criteria:

• Hypertension (BP >140/90) present at screening;
• Multifetal gestation;
• Type 1 or Type 2 diabetes antedating pregnancy;
• SLE patients requiring prednisone >10 mg/day;
• Platelet count <100,000 per microliter;
• Women currently taking prednisone greater than 10 mg daily;
• Women with urinary excretion with greater than 500 mg (0.5 g) per day (spot urine protein/creatinine ration 0.5);
• Serum creatinine >1.2 mg/dL
• History of tuberculosis or untreated positive PPD;
• Women with a tuberculin skin test induration of 5 mm or greater; or positive quantiFERON-gold test
• Women with HIV, Hepatitis B or Hepatitis C positive status;

• Known contraindications or relative contraindications to certolizumab:

  1. Active infection, e.g., chronic hepatitis B
  2. History of recurrent infection, e.g., recurrent cellulitis, or opportunistic infection
  3. History of prior active/treated endemic mycoses in the last two years (including coccidioidomycosis, blastomycosis, or histoplasmosis)
  4. History of heart failure
  5. History of peripheral demyelinating disease or Guillian-Barre syndrome
  6. History of hematologic malignancy
  7. Prior adverse reaction to certolizumab or o ther anti-TNF-α agent

Contact Information

Project Coordinator
Marta M. Guerra, M.S.
212.774.7361
guerram@hss.edu