A Trial of Antenatal Treatment of Alloimmune Thrombocytopenia

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00194987
• Collaborator: New York Presbyterian Hospital (Other), Columbia University (Other)
• Enrollment: 102
• Location: 1
• Arms: 2
• Duration (Months): 170.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purposes of this study are to provide medical management by giving treatment to the mother that will bring up the fetal platelet count and to minimize the number of invasive procedures to the fetus (which may result in serious fetal injuries).

Condition or Disease	Intervention/Treatment	Phase
Alloimmune Thrombocytopenia; Fetal Alloimmune Thrombocytopenia	Drug: IVIG (Intravenous Immunoglobulin); Drug: prednisone	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomization between 2 groupsrandomization between 2 groups
• Masking: None (Open Label)
• Masking Description: participants and their physicians will know if they are receiving IVIG x 2 or IVIG x1 plus prednisone
• Primary Purpose: Treatment
• Official Title: A Randomized Multicenter Trial of Antenatal Treatment of Alloimmune Thrombocytopenia
• Study Start Date: Apr 1, 2001
• Actual Primary Completion Date: Jun 30, 2015
• Actual Study Completion Date: Jun 30, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IVIG x 2 IVIG 2 g/kg/wk divided into 2 infusions per week for women with a fetus affected by FNAIT	Drug: IVIG (Intravenous Immunoglobulin); one gram per kg of IVIG per infusion given either once or twice
Experimental: IVIG x 1 + prednisone IVIG 1 g/kg/wk in 1 infusion per week + prednisone 0.5 mg po daily for women with a fetus affected by FNAIT	Drug: IVIG (Intravenous Immunoglobulin); one gram per kg of IVIG per infusion given either once or twice; Drug: prednisone; in arm with IVIG 1 gm/kg/wk will also receive prednisone 0.5 mg/kg/day

Outcome Measures

Primary Outcome Measures

1. Number of Newborns With a Birth Platelet Count > 50,000/uL [32-40 weeks (the endpoint is the birth which is not at the same number of weeks for all of the babies. This is why the weeks are not listed specifically eg week 40]

   this uses the birth platelet count of the fetuses from the study when they are born

Secondary Outcome Measures

1. Intracranial Hemorrhage: Number Occurring in Fetuses and Newborns of Mothers in Study [time of ICH (range 20-40 wks)]

   number of ICH assessed by fetal and neonatal ultrasound with MRI back up most commonly in utero so range from 20-40 weeks fo gestation

2. Number of Fetal Platelet Counts > 50,000/uL [32 +/- 2 weeks]

   Number of Fetal Platelet Counts > 50,000/uL Among Those Who Underwent Fetal Blood Sampling and Had a Fetal Platelet Count Determined

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Pregnant women are eligible for inclusion into the Very High Risk Group if they:

• are PLA-1 (platelet antigen A1) negative and have known platelet incompatibility with their fetus

• have had a previous child who suffered an antenatal hemorrhage prior to 28 weeks gestation (as best as could be estimated)

• are less than 19 weeks gestation

Pregnant women are eligible for inclusion into the High Risk Group if they:

• are PLA-1 negative and have known platelet incompatibility with the fetus

• have had a previous child who suffered an antenatal hemorrhage after 28 weeks gestation (as best as could be estimated)

• are between 12-30 weeks gestation

Pregnant women are eligible for inclusion into the Standard Risk Group if they:

• are PLA-1 negative and have known platelet incompatibility with the fetus

• have not had a previous child who suffered an antenatal hemorrhage

• are between 20-30 weeks gestation

Exclusion Criteria:

Women are not eligible for inclusion into the Very High Risk Group if they:

• have had a previous child who suffered an antenatal hemorrhage after 28 weeks gestation

• are greater than 19 weeks gestation

Women are not eligible for inclusion into the High Risk Group if they:

• have had a previous child who suffered an antenatal hemorrhage prior to 28 weeks gestation

• are greater than 30 weeks gestation

Women are not eligible for inclusion into the Standard Risk Group if they:

• have had a previous child who suffered an antenatal hemorrhage

• are greater than 30 weeks gestation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York Presbyterian Hospital-Weill Cornell Medical Center	New York	New York	United States	10021

Sponsors and Collaborators

• Weill Medical College of Cornell University
• New York Presbyterian Hospital
• Columbia University

Investigators

• Principal Investigator: James B Bussel, M.D., Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00194987
• Other Study ID Numbers: 0102004801
• First Posted: Sep 19, 2005
• Last Update Posted: Nov 7, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Weill Medical College of Cornell University: Alloimmune thrombocytopenia; Fetal alloimmune thrombocytopenia
• Additional relevant MeSH terms: Thrombocytopenia; Prednisone; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; gamma-Globulins; Rho(D) Immune Globulin

Study Results

Participant Flow

Recruitment Details	pregnant women with a fetus affected by FNAIT were enrolled at multiple sites with local IRB permission and local consents fetuses were tracked in utero and after birth for 2 weeks

Arm/Group Title	Intravenous Gammglobulin (IVIG) 1g/kg Twice Per Week	IVIG 1g/k/Week and Prednisone 0.5 mg/kg/Day
Arm/Group Description	51 women entered the study and received IVIG 1g/kg twice per week rounded off to the nearest 5-10 kg. The initial treatment weight was used throughout. premeds were diphenhydramine, acetaminophen and single dose prednisone as needed if the fetal platelet count was < 50,000/ul or not obtained at approximately 32 weeks of gestation either for technical reasons or parental refusal, prednisone 0.5mg/kg/day was added to the continued IVIG infusions delivery was primarily by Caesarean section unless the fetal count was known or strongly suspected to be (> 50,000 all women had fetal and neonatal alloimmune thrombocytopenia with a previous affected pregnancy and virtually all had parental incompatibility of HPA-1a ultrasound of the fetus was performed every 4 weeks or so and postnatally neonatal platelet counts were obtained and treatment of the fetus with platelet transfusion and/or IVIG and/or steroids was given as needed as determined by the NICU staff where the baby was delivered	IVIG was infused at 1 gram/kg/week rounded off to the nearest 5-10 kg. The initial treatment weight was used throughout. premeds were diphenhydramine, acetaminophen and single dose prednisone as needed all women had fetal and neonatal alloimmune thrombocytopenia with a previous affected pregnancy and were known to be carrying an affected fetus treatment was initiated at approximately 20-26 weeks of gestation at approximately 32 weeks of gestation a fetal platelet count was obtained if the fetal platelet count was < 50,000/ul or was not obtained for either technical difficulty or patient refusal, then a second 1g/kg/week of IVIG was added until delivery delivery was typically by C/S unless the fetal platelet count was known or strongly suspected to be > 50,000/up neonatal platelet counts were obtained and treatment of the fetus with platelet transfusion and/or IVIG and/or steroids was given as needed as determined by the NICU staff where the baby was delivered
Period Title: Overall Study
STARTED	51	51
COMPLETED	51	48
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	IVIG (Intravenous Gamma Globulin) 2g/kg/Week	IVIG 1g/kg/wk and Prednisone 0.5mg/kg/Day	Total
Arm/Group Description	pregnant women with alloimmune thrombocytopenia and a previous affected fetus/newborn and a current affected fetus starting IVIG 2 g/kg/week	pregnant women with alloimmune thrombocytopenia and a previous affected fetus/newborn and a current affected fetus starting IVIG 1 g/kg/week + prednisone 0.5mg/kg/day	Total of all reporting groups
Overall Participants	51	51	102
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	51 100%	51 100%	102 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	51 100%	51 100%	102 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	48 94.1%	46 90.2%	94 92.2%
Canada	3 5.9%	5 9.8%	8 7.8%

Outcome Measures

1. Primary Outcome

Title	Number of Newborns With a Birth Platelet Count > 50,000/uL
Description	this uses the birth platelet count of the fetuses from the study when they are born
Time Frame	32-40 weeks (the endpoint is the birth which is not at the same number of weeks for all of the babies. This is why the weeks are not listed specifically eg week 40

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVIG 1g/kg Twice Per Week	IVIG 1g/k/Week and Prednisone 0.5 mg/kg/Day
Arm/Group Description	51 women entered the study and received IVIG 1g/kg twice per week rounded off to the nearest 5-10 kg. The initial treatment weight was used throughout. premeds were diphenhydramine, acetaminophen and single dose prednisone as needed if the fetal platelet count was < 50,000/ul or not obtained at approximately 32 weeks of gestation either for technical reasons or parental refusal, prednisone 0.5mg/kg/day was added to the continued IVIG infusions delivery was primarily by Caesarean section unless the fetal count was known or strongly suspected to be (> 50,000 all women had fetal and neonatal alloimmune thrombocytopenia with a previous affected pregnancy and virtually all had parental incompatibility of HPA-1a ultrasound of the fetus was performed every 4 weeks or so and postnatally neonatal platelet counts were obtained and treatment of the fetus with platelet transfusion and/or IVIG and/or steroids was given as needed as determined by the NICU staff where the baby was delivered	IVIG was infused at 1 gram/kg/week rounded off to the nearest 5-10 kg. The initial treatment weight was used throughout. premeds were diphenhydramine, acetaminophen and single dose prednisone as needed all women had fetal and neonatal alloimmune thrombocytopenia with a previous affected pregnancy and were known to be carrying an affected fetus treatment was initiated at approximately 20-26 weeks of gestation at approximately 32 weeks of gestation a fetal platelet count was obtained if the fetal platelet count was < 50,000/ul or was not obtained for either technical difficulty or patient refusal, then a second 1g/kg/week of IVIG was added until delivery delivery was typically by C/S unless the fetal platelet count was known or strongly suspected to be > 50,000/up neonatal platelet counts were obtained and treatment of the fetus with platelet transfusion and/or IVIG and/or steroids was given as needed as determined by the NICU staff where the baby was delivered
Measure Participants	51	51
Number [number of newborns with >50,000 pets]	48	47

2. Secondary Outcome

Title	Intracranial Hemorrhage: Number Occurring in Fetuses and Newborns of Mothers in Study
Description	number of ICH assessed by fetal and neonatal ultrasound with MRI back up most commonly in utero so range from 20-40 weeks fo gestation
Time Frame	time of ICH (range 20-40 wks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVIG 1g/kg Twice Per Week	IVIG 1g/k/Week and Prednisone 0.5 mg/kg/Day
Arm/Group Description	51 women entered the study and received IVIG 1g/kg twice per week rounded off to the nearest 5-10 kg. The initial treatment weight was used throughout. premeds were diphenhydramine, acetaminophen and single dose prednisone as needed if the fetal platelet count was < 50,000/ul or not obtained at approximately 32 weeks of gestation either for technical reasons or parental refusal, prednisone 0.5mg/kg/day was added to the continued IVIG infusions delivery was primarily by Caesarean section unless the fetal count was known or strongly suspected to be (> 50,000 all women had fetal and neonatal alloimmune thrombocytopenia with a previous affected pregnancy and virtually all had parental incompatibility of HPA-1a ultrasound of the fetus was performed every 4 weeks or so and postnatally neonatal platelet counts were obtained and treatment of the fetus with platelet transfusion and/or IVIG and/or steroids was given as needed as determined by the NICU staff where the baby was delivered	IVIG was infused at 1 gram/kg/week rounded off to the nearest 5-10 kg. The initial treatment weight was used throughout. premeds were diphenhydramine, acetaminophen and single dose prednisone as needed all women had fetal and neonatal alloimmune thrombocytopenia with a previous affected pregnancy and were known to be carrying an affected fetus treatment was initiated at approximately 20-26 weeks of gestation at approximately 32 weeks of gestation a fetal platelet count was obtained if the fetal platelet count was < 50,000/ul or was not obtained for either technical difficulty or patient refusal, then a second 1g/kg/week of IVIG was added until delivery delivery was typically by C/S unless the fetal platelet count was known or strongly suspected to be > 50,000/up neonatal platelet counts were obtained and treatment of the fetus with platelet transfusion and/or IVIG and/or steroids was given as needed as determined by the NICU staff where the baby was delivered
Measure Participants	51	51
Number [number of newborns with ICH]	0	0

3. Secondary Outcome

Title	Number of Fetal Platelet Counts > 50,000/uL
Description	Number of Fetal Platelet Counts > 50,000/uL Among Those Who Underwent Fetal Blood Sampling and Had a Fetal Platelet Count Determined
Time Frame	32 +/- 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVIG 1g/kg Twice Per Week	IVIG 1g/k/Week and Prednisone 0.5 mg/kg/Day
Arm/Group Description	51 women entered the study and received IVIG 1g/kg twice per week rounded off to the nearest 5-10 kg. The initial treatment weight was used throughout. premeds were diphenhydramine, acetaminophen and single dose prednisone as needed if the fetal platelet count was < 50,000/ul or not obtained at approximately 32 weeks of gestation either for technical reasons or parental refusal, prednisone 0.5mg/kg/day was added to the continued IVIG infusions delivery was primarily by Caesarean section unless the fetal count was known or strongly suspected to be (> 50,000 all women had fetal and neonatal alloimmune thrombocytopenia with a previous affected pregnancy and virtually all had parental incompatibility of HPA-1a ultrasound of the fetus was performed every 4 weeks or so and postnatally neonatal platelet counts were obtained and treatment of the fetus with platelet transfusion and/or IVIG and/or steroids was given as needed as determined by the NICU staff where the baby was delivered	IVIG was infused at 1 gram/kg/week rounded off to the nearest 5-10 kg. The initial treatment weight was used throughout. premeds were diphenhydramine, acetaminophen and single dose prednisone as needed all women had fetal and neonatal alloimmune thrombocytopenia with a previous affected pregnancy and were known to be carrying an affected fetus treatment was initiated at approximately 20-26 weeks of gestation at approximately 32 weeks of gestation a fetal platelet count was obtained if the fetal platelet count was < 50,000/ul or was not obtained for either technical difficulty or patient refusal, then a second 1g/kg/week of IVIG was added until delivery delivery was typically by C/S unless the fetal platelet count was known or strongly suspected to be > 50,000/up neonatal platelet counts were obtained and treatment of the fetus with platelet transfusion and/or IVIG and/or steroids was given as needed as determined by the NICU staff where the baby was delivered
Measure Participants	51	51
Number [number newborns with >50,000 pats]	44	43

Adverse Events

Time Frame	collected for study women from 20 weeks of gestation until 2 weeks after birth of newborn fetus and newborns were collected for the same period of time
Arm/Group Title	IVIG X 2 Weekly		IVIG 1 g/kg/wk + Prednisone		IVIG X 2 Weekly--fetuses/Newborns		IVIG x 1 + Prednisone---fetuses/Newborns
Arm/Group Description	Intravenous Immunoglobulin (IVIG) one gram per kg bodyweight infused twice weekly to mothers during pregnancy fetuses followed by serial ultrasound including after birth and newborns followed for 2 or so weeks after birth		intravenous gammaglobulin 1 g/kg/wk infused once weekly to mother and prednisone 0.5 mg/kg/day taken by mothers during pregnancy and then tapered after birth fo newborn fetuses followed by serial ultrasound including after birth and newborns followed for 2 or so weeks after birth		fetuses and newborns of mother receiving IVIG x 2 weekly		fetuses and newborns of mother receiving IVIG x 1 weekly + prednisone 0.5mg/kg daily
All Cause Mortality
	IVIG X 2 Weekly		IVIG 1 g/kg/wk + Prednisone		IVIG X 2 Weekly--fetuses/Newborns		IVIG x 1 + Prednisone---fetuses/Newborns
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/51 (0%)		0/51 (0%)		0/51 (0%)
Serious Adverse Events
	IVIG X 2 Weekly		IVIG 1 g/kg/wk + Prednisone		IVIG X 2 Weekly--fetuses/Newborns		IVIG x 1 + Prednisone---fetuses/Newborns
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/51 (27.5%)		12/51 (23.5%)		4/51 (7.8%)		3/51 (5.9%)
Blood and lymphatic system disorders
thrombosis, venous	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Endocrine disorders
gestational diabetes	2/51 (3.9%)	2	4/51 (7.8%)	4	0/51 (0%)	0	0/51 (0%)	0
diabetes mellitus	0/51 (0%)	0	3/51 (5.9%)	3	0/51 (0%)	0	0/51 (0%)	0
Infections and infestations
amnionitis	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
neonatal sepsis	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Nervous system disorders
headache	4/51 (7.8%)	4	2/51 (3.9%)	2	0/51 (0%)	0	0/51 (0%)	0
fetal ICH	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Pregnancy, puerperium and perinatal conditions
preterm labor	5/51 (9.8%)	5	2/51 (3.9%)	2	0/51 (0%)	0	0/51 (0%)	0
HELLP	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
premature delivery	4/51 (7.8%)	4	3/51 (5.9%)	3	4/51 (7.8%)	4	3/51 (5.9%)	3
Psychiatric disorders
depression	1/51 (2%)	1	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
Other (Not Including Serious) Adverse Events
	IVIG X 2 Weekly		IVIG 1 g/kg/wk + Prednisone		IVIG X 2 Weekly--fetuses/Newborns		IVIG x 1 + Prednisone---fetuses/Newborns
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/51 (23.5%)		8/51 (15.7%)		0/51 (0%)		0/51 (0%)
Endocrine disorders
diabetes mellitus	0/51 (0%)	0	2/51 (3.9%)	2	0/51 (0%)	0	0/51 (0%)	0
neonatal hypoglycemia	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Musculoskeletal and connective tissue disorders
jaw tightness	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
Nervous system disorders
bells palsy	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0	0/51 (0%)	0
headache	5/51 (9.8%)	5	2/51 (3.9%)	2	0/51 (0%)	0	0/51 (0%)	0
Pregnancy, puerperium and perinatal conditions
hypertension	3/51 (5.9%)	3	2/51 (3.9%)	2	0/51 (0%)	0	0/51 (0%)	0
Product Issues
IVIG dose error	2/51 (3.9%)	2	2/51 (3.9%)	2	0/51 (0%)	0	0/51 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.