Eculizumab Use in the Postpartum Period for the Treatment of Pregnancy Associated aHUS: A Case Series

NCT03574506 | Unknown DMC

• 1 other identifier: LS30885-1
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Eculizumab is a humanized monoclonal IgG antibody against protein C5 that works to inhibit the activation of the terminal complement cascade. The Eculizumab is currently FDA approved for the treatment of Paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (aHUS) and has been shown to improve the quality of life and overall survival in these patients. aHUS is a life-threatening disease of complement mediated thrombotic microangiopathy often triggered by an inciting event, such as an infection or immunocompromised state. Pregnancy has also been identified as an inciting event, with patients most often experiencing aHUS in the postpartum period. Due to its rare nature, pregnancy-associated aHUS is often mistaken for preeclampsia or hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome. As standard treatment for preeclampsia and HELLP syndrome is completion of the pregnancy by expediting delivery of the baby. A missed diagnosis of aHUS can result in delays in treatment, including use of Eculizumab when appropriate; such delay can increase the risk of maternal morbidity and mortality. When aHUS is suspected in the postpartum period, Eculizumab could be initiated early; however, there is limited data on use of Eculizumab in this setting.

Conditions

Atypical Hemolytic Uremic Syndrome; Pregnancy

Keywords

Atypical Hemolytic Uremic Syndrome; Pregnancy

Outcome Measures

Primary Outcomes (1)

• Maternal mortality

  Death of a woman within 42 days of termination of pregnancy. This is a dichotomy measure

  The data collection will be among the first postpartum day until the sixth month

Secondary Outcomes (2)

• ICU length of stay

  The data collection will be among the first postpartum day until the sixth month

• Dosing and number of doses received

  The data collection will be among the first postpartum day until the sixth month

Eligibility Criteria

• Age: 14 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Postpartum patients meeting diagnostic criteria for pregnancy associated aHUS between January 2009 and May 2016 in Colombia. This study cohort will be stratified into two groups: 1) women with suspected postpartum aHUS treated with Eculizumab and; 2) women meeting diagnostic criteria for postpartum aHUS that did not receive treatment with Eculizumab. We chose a start date of 2009 because this was the year that Eculizumab was approved by the National Institute of Food and Drug Monitoring (INVIMA) for use in Paroxysmal Nocturnal Hemoglobinuria (PNH). Eculizumab was subsequently approved for use in aHUS in 2011. We also seek to identify a matched cohort of women diagnosed with pregnancy associated aHUS in Colombia in the same time frame who did not receive Eculizumab treatment.

You may qualify if:

• All patients in the postpartum period (within 12 weeks of delivery) that were diagnosed with aHUS by their treating provider or who met standard diagnostic criteria.
• Subjects meeting diagnostic criteria for aHUS will be included in the study independent of the treatment approach employed by their providers.
• Those who received at least one dose of Eculizumab for treatment of suspected aHUS will be included, regardless of outcome.

You may not qualify if:

• Patients who did not authorize the use of their information after an informed consent process
• Patients who their physicians who did not agree to participate in or provide patient information.

Sponsors & Collaborators

• Fundación Grupo de Investigación en Cuidados Intensivos y Obstetricia: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Gestion Salud

Cartagena, Departamento de Bolívar, 130015, Colombia

Location

Related Publications (8)

• Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009 Oct 22;361(17):1676-87. doi: 10.1056/NEJMra0902814. No abstract available.

  PMID: 19846853 BACKGROUND

• Fakhouri F, Hourmant M, Campistol JM, Cataland SR, Espinosa M, Gaber AO, Menne J, Minetti EE, Provot F, Rondeau E, Ruggenenti P, Weekers LE, Ogawa M, Bedrosian CL, Legendre CM. Terminal Complement Inhibitor Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial. Am J Kidney Dis. 2016 Jul;68(1):84-93. doi: 10.1053/j.ajkd.2015.12.034. Epub 2016 Mar 21.

  PMID: 27012908 BACKGROUND

• Kelly RJ, Hochsmann B, Szer J, Kulasekararaj A, de Guibert S, Roth A, Weitz IC, Armstrong E, Risitano AM, Patriquin CJ, Terriou L, Muus P, Hill A, Turner MP, Schrezenmeier H, Peffault de Latour R. Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2015 Sep 10;373(11):1032-9. doi: 10.1056/NEJMoa1502950.

  PMID: 26352814 BACKGROUND

• Kelly RJ, Hill A, Arnold LM, Brooksbank GL, Richards SJ, Cullen M, Mitchell LD, Cohen DR, Gregory WM, Hillmen P. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011 Jun 23;117(25):6786-92. doi: 10.1182/blood-2011-02-333997. Epub 2011 Apr 1.

  PMID: 21460245 BACKGROUND

• Fakhouri F, Roumenina L, Provot F, Sallee M, Caillard S, Couzi L, Essig M, Ribes D, Dragon-Durey MA, Bridoux F, Rondeau E, Fremeaux-Bacchi V. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol. 2010 May;21(5):859-67. doi: 10.1681/ASN.2009070706. Epub 2010 Mar 4.

  PMID: 20203157 BACKGROUND

• Tsai HM, Kuo E. From Gestational Hypertension and Preeclampsia to Atypical Hemolytic Uremic Syndrome. Obstet Gynecol. 2016 May;127(5):907-910. doi: 10.1097/AOG.0000000000001340.

  PMID: 27054930 BACKGROUND

• Vaught AJ, Gavriilaki E, Hueppchen N, Blakemore K, Yuan X, Seifert SM, York S, Brodsky RA. Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome. Exp Hematol. 2016 May;44(5):390-8. doi: 10.1016/j.exphem.2016.01.005. Epub 2016 Feb 26.

  PMID: 26921648 BACKGROUND

• Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA. 2000 May 24-31;283(20):2701-11. doi: 10.1001/jama.283.20.2701.

  PMID: 10819955 BACKGROUND

MeSH Terms

Conditions

Atypical Hemolytic Uremic Syndrome

Condition Hierarchy (Ancestors)

Hemolytic-Uremic Syndrome; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia

Study Officials

• Jose A Rojas, MD. Msc

  Fundacion GRICIO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: July 2, 2018
• Study Start: April 15, 2018
• Primary Completion: August 30, 2020
• Study Completion: November 30, 2020
• Last Updated: June 2, 2020

Record last verified: 2020-05

Locations

CO (1)