Clinical Study of Caffeine for Apnea of Prematurity - Full Text View

Purpose

The aim of the present Phase III study is to evaluate the safety, efficacy and pharmacokinetics of Caffeine Citrate for treatment of apnea of prematurity in Japan.

Condition	Intervention	Phase
Apnea of Prematurity	Drug: NPC-11 for intravenous or oral administration.	Phase 3


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	A Phase III Clinical Study of NPC-11 in the Treatment of Apnea of Prematurity. - Investigation of Safety, Efficacy and Pharmacokinetics of Caffeine Citrate -

Resource links provided by NLM:

MedlinePlus related topics: Caffeine

Drug Information available for: Sodium citrate

U.S. FDA Resources

Further study details as provided by Nobelpharma:

Primary Outcome Measures:

Success rates for controlling of apnea episode in each observation day (at least 50% reduction of apnea episodes from baseline) [ Time Frame: 1, 2, 3, 4, 5, 6,7, 8, 9 and 10 day ]

Secondary Outcome Measures:

The change of frequency of apnea episode from baseline in each observation day [ Time Frame: 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 day ]
Time to event：Days until next events occurred [ Time Frame: 1 to 10 day ]
Time to event：Days until next events occurred.

The definition of events are, Not at least 50% reduction of apnea episode Not improving the frequency of episode from baseline Needs mechanical/bag valve mask ventilation.
The change of average duration time of apnea episode from baseline in each observation day [ Time Frame: 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 day ]
The change of lowest oxygen saturation during apnea episodes from baseline in each observation day [ Time Frame: 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 day ]
The proportion of less than 85% oxygen saturation during apnea episodes in each observation day [ Time Frame: 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 day ]


Enrollment:	24
Study Start Date:	August 2011
Study Completion Date:	October 2012
Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: NPC-11 Loading Dose (Day 1): Caffeine citrate 20 mg/kg body weight will be administered intravenously using a syringe infusion pump over 30 minutes. Maintenance Dose (Day 2～Day 10): After an interval 24 hours, caffeine citrate 5 mg/kg body weight will be administered intravenously (over 10 minutes) or orally if the patients will be able to receive oral administration once a day. The maintenance dose can be increased to a maximum 10 mg/kg caffeine citrate once a day if apnea persists.	Drug: NPC-11 for intravenous or oral administration. NPC-11, Each vial (3mL) contains 60 mg caffeine citrate (equivalent to 30mg caffeine). Other Name: caffeine citrate

Arms

Assigned Interventions

Experimental: NPC-11

Loading Dose (Day 1): Caffeine citrate 20 mg/kg body weight will be administered intravenously using a syringe infusion pump over 30 minutes.
Maintenance Dose (Day 2～Day 10): After an interval 24 hours, caffeine citrate 5 mg/kg body weight will be administered intravenously (over 10 minutes) or orally if the patients will be able to receive oral administration once a day. The maintenance dose can be increased to a maximum 10 mg/kg caffeine citrate once a day if apnea persists.

Drug: NPC-11 for intravenous or oral administration.

NPC-11, Each vial (3mL) contains 60 mg caffeine citrate (equivalent to 30mg caffeine).

Other Name: caffeine citrate

Eligibility


Ages Eligible for Study:	28 Weeks to 33 Weeks (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Postconceptional age between 28 weeks and 33 weeks, and over 24 hours after birth.
At least 6 episodes of apnea (>20 seconds in duration) in 24 hours.
Signed written informed consent from parent(s) or legal guardian(s).

Exclusion Criteria:

Apnea due to: hypoxic-ischemic encephalopathy, meningitis, seizures, Grade III or IV intracranial hemorrhage, CNS depression from drugs administered to the mother during delivery, periventricular leukomalacia, pneumonia which does not improve even if it treats, hemoglobin< 10 g/dL, sepsis, shock which does not improve even if it treats, blood pH<7.2 on 2 consecutive determinations in spite of correction, serum calcium concentration <7.0 mg/dL which does not improve even if it treats, serum glucose concentration <4.0 mg/dL which does not improve even if it treats, congestive heart failure, symptomatic patent ductus arteriosus, rectal temperature＞38.5 °C on 2 consecutive readings, rectal temperature< 35 °C on 2 consecutive readings, obstructive apnea.
Blood urea nitrogen >20 mg/dL, serum creatinine >1.5 mg/dL.
Serum AST or ALT >3 times the upper limit of normal.
Requirement of mechanically-assisted ventilation ( containing nasal CPAP, nasal DPAP).
Previous treatment with methylxanthines within 7 days prior to study enrollment.
Previous treatment with H2 antagonists (i.e., cimetidine or ranitidine) within 7 days prior to study enrollment.
Receiving or experiencing the effects of CNS-active medication at the time of enrollment.
Participant of other clinical trial within 6 months.
Inappropriate to enter this clinical trial judged by the investigator in charge.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01408173

Locations


Japan
Fujita Health University Hospital
Kutsukake, Aichi, Japan
Osaka Medical Center and Research Institute for Maternal and Child Health
Izumi, Osaka, Japan
Tokyo Metropolitan Children's Medical Center
Fuchu, Tokyo, Japan

Sponsors and Collaborators

Nobelpharma

Investigators


Principal Investigator:	Susumu Itoh, MD, PhD	Kagawa University

More Information


Responsible Party:	Nobelpharma
ClinicalTrials.gov Identifier:	NCT01408173 History of Changes
Other Study ID Numbers:	NPC-11-1
Study First Received:	July 29, 2011
Last Updated:	October 29, 2013

Keywords provided by Nobelpharma:


caffeine apnea prematurity

Additional relevant MeSH terms:


Apnea Premature Birth Respiration Disorders Respiratory Tract Diseases Signs and Symptoms, Respiratory Signs and Symptoms Obstetric Labor, Premature Obstetric Labor Complications Pregnancy Complications Citric Acid Caffeine Caffeine citrate Anticoagulants	Calcium Chelating Agents Chelating Agents Sequestering Agents Molecular Mechanisms of Pharmacological Action Central Nervous System Stimulants Physiological Effects of Drugs Phosphodiesterase Inhibitors Enzyme Inhibitors Purinergic P1 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents

ClinicalTrials.gov processed this record on August 22, 2017