Metabolic AcidosisPhase 3PROTECTNCT06545565
Prevention of Metabolic Acidosis in Preterm Neonates by Replacing Sodium Chloride With Sodium Acetate in Parenteral Nutrition
A Phase 3 study testing sodium acetate group will receive sodium acetate in the neonatal PN. and sodium chloride group will receive sodium chloride in the neonatal PN. in people with Metabolic Acidosis and Neonatal Disease, run by Aga Khan University Hospital, Pakistan at 1 site in Pakistan.
Trial summary
The goal of this clinical trial is to learn if the addition of sodium acetate in neonatal PN works to prevent and treat metabolic acidosis and associated comorbidities in preterm neonates. It will also teach about the optimal doses of sodium acetate in PN. Read more about this study
- Who is it for?
- Ages 1 day to 3 daysHealthy volunteers can take part
- Conditions the study is for
- Metabolic Acidosis, Neonatal Disease, Neonatal Complication
- What is being tested?
- sodium acetate group will receive sodium acetate in the neonatal PN. and sodium chloride group will receive sodium chloride in the neonatal PN.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 sitePakistan
- Study dates
- 10 Jul 2024to 10 May 2025
- Phase
- Phase 3
- 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 1 day to 3 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Written informed consent obtained by parents/legal representative (according to local regulations) before the initiation of PN.
- All the neonates who were admitted to the NICU of AKUH and received PN during 28 days of their life.
- Gestational age < 33 weeks
Who cannot join
- Infants with an inborn error of metabolism
- Genetic or congenital condition that affects neurodevelopment or requires multiple surgeries (e.g., congenital viral infection, hydrops, complex congenital heart disease, severe dysmorphic features, etc.)
- Severe metabolic alkalosis, in critically ill neonates, is defined as a persistent elevation of the serum pH above 7.45 and it also involves a primary increase in serum bicarbonate (HCO3-) concentration > 25mEq/L.
- Severe Hypernatremia, in critically ill neonates, is defined as persistently high serum sodium levels > 150 mmol/L
- Severe liver failure and syndromic infants with multiple congenital abnormalities and severe perinatal asphyxia
- -
Trial locations and contacts
1 site in 1 country.
Adnan Mirza, MBBS contact
Pakistan1 site, 1 recruiting
- Recruiting
Aga Khan University Hospital
Karachi, Sindh, 74800
Gul Ambreen, PhD, +92 3002402035, gul.ambreen@aku.edu
Adnan Mirza, MBBS, adnan.mirza@aku.edu
About this study
Official title: Prevention of Metabolic Acidosis in Preterm Neonates by Replacing Sodium Chloride With Sodium Acetate in Parenteral Nutrition - A Randomized Controlled Trial. (PROTECT Trial)
The goal of this clinical trial is to learn if the addition of sodium acetate in neonatal PN works to prevent and treat metabolic acidosis and associated comorbidities in preterm neonates. It will also teach about the optimal doses of sodium acetate in PN. The main questions it aims to answer are:
Is the incidence of metabolic acidosis reduced in preterm neonates who received daily Sodium acetate in PN therapy (treatment) during the initial weeks of life compared with individuals who received sodium chloride in PN (standard)? Is the rate of neonatal comorbidities reduced in preterm neonates who received daily Sodium acetate in PN therapy (treatment) during the initial weeks of life compared with individuals who received sodium chloride in PN (standard)? What are the optimal neonatal dosing recommendations/guidelines of sodium acetate in daily PN, which are required to prevent/treat metabolic acidosis in the early life of preterm neonates? Researchers will compare Sodium acetate in PN therapy to sodium chloride in PN to see if Sodium acetate works to prevent and treat metabolic acidosis and associated comorbidities.
Read more
Included Participants:
All the neonates were admitted to the NICU of AKUH and received PN during 28 days of their lives.
Participants will receive sodium acetate or sodium chloride Written informed consent was obtained by parents/legal representatives (according to local regulations) before the initiation of PN. Gestational age < 33 weeks Included in the study before 72 hours of life
Read the detailed description
Background Providing optimal nutritional support to extremely preterm and very low birth weight (VLBW) infants is still very much a challenge, as enteral feeding is generally delayed due to the prematurity of gastrointestinal function; these infants have poor sucking and swallowing reflexes, and there are concerns that a liberal feeding strategy may lead to complications, such as feeding intolerance or necrotizing enterocolitis (NEC). Early nutritional support is primarily delivered through parenteral nutrition (PN) is essential in the critical management during the neonatal period in these preterm babies.
PN provides all the required nutritional needs of preterm, including fluid, calories, and electrolytes. Sodium is both an electrolyte and a mineral. It helps keep the water (the amount of fluid inside and outside the body's cells) and electrolyte balance of the body. Sodium is also important in how nerves and muscles work. Most of the sodium in the body (about 85%) is found in blood and lymph fluid. Sodium is also provided through PN in two forms The first form is sodium chloride. In most parts of the world, sodium supplementation in PN has largely been in the form of sodium chloride. This is also the standard of care in the neonatal intensive care unit of Aga Khan University Hospital. Sodium chloride is added to the PN according to the sodium levels and body fluid balance.
The second source of sodium is sodium acetate, which is new in Aga Khan University Hospital but internationally used in PN. Daily sodium acetate will be added to the PN bag according to the sodium levels, acid-base balance, and total fluid intake. With the addition of sodium acetate, neonates have fewer metabolic acidosis complications, are more effective in preventing comorbidities, and are being used in the NICUs of developed countries.
MATERIALS AND METHODS Design This will be a 2-arm open-label phase III randomized controlled trial (RCT) to compare Sodium acetate and Sodium chloride, given daily as the component of parenteral nutrition over during first 28 days of life. Investigators will initiate the treatment within the first 72 hours following birth.
Setting This study will be conducted in the Neonatal Intensive Care Unit (NICU) of the Aga Khan University Hospital (AKUH), which is a 700-bedded, not-for-profit tertiary care hospital receiving country-wide referrals.
The interventional group: This group will receive sodium acetate in the neonatal PN.
Control Group: The control group will receive sodium chloride in the neonatal PN.
Intervention of the study: Use of sodium acetate in neonatal PN.
Data collection:
All relevant maternal and infant demographic data/Baseline characteristics, blood investigation results, and clinical outcomes will be recorded prospectively. The primary outcomes, pH, and base excess (BE) will be recorded from pre-PN on the first day of life (DOL), then 2- 7 DOL, and days 10, 13, 16,20,25, and 28 of life. For infants requiring less than 28 days of hospital stay, data will be collected till discharge/death.
- Conditions
- Metabolic Acidosis, Neonatal Disease, Neonatal Complication
- Being tested
- sodium acetate group will receive sodium acetate in the neonatal PN., sodium chloride group will receive sodium chloride in the neonatal PN.
- Keywords
- metabolic acidosis, sodium acetate, neonates, Parenteral Nutrition
- Medical subject headings
- Acidosis, Infant, Newborn, Diseases, Hyperphagia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium acetate group will receive sodium acetate in the neonatal PN.Drug
Also called Sodium Acetate
This group will receive sterile sodium acetate daily in the neonatal PN for the duration the patient will receive parenteral nutrition, a maximum of 28 days of life.
sodium chloride group will receive sodium chloride in the neonatal PN.Drug
Also called sodium Chloride
This group will receive sterile sodium chloride daily in the neonatal PN for the duration the patient will receive parenteral nutrition, a maximum of 28 days of life.
| Study group | Role | What they receive |
|---|---|---|
| sodium acetate | Experimental | Not described Receives: Drug: sodium acetate group will receive sodium acetate in the neonatal PN. |
| Sodium Chloride | Active comparator | Not described Receives: Drug: sodium chloride group will receive sodium chloride in the neonatal PN. |
What is being measured
The primary outcome is the main question the study is designed to answer.
metabolic acidosis
Severe metabolic acidosis, in critically ill neonates, is defined as a persistent low Blood pH < 7.26 and it also involves a primary decrease in serum bicarbonate (HCO3-) concentration <16 mEq/L]
Measured: Blood-ph and serum-bicarbonate concentration will be recorded from pre-PN on the first day of life (DOL), then 2-7 DOL, and days 10,13,16,20,25&28 of life. For infants requiring <28 days of hospital stay until discharge/death.
Secondary outcomes (5)
Development of Comorbid conditions (Bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), Intraventricular hemorrhage (IVH), Retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), Sepsis and jaundice ).
Measured: From the date of randomization until the date of first documented comorbid condition, assessed up to 28 days of life or date of death from any cause, whichever came first.
Duration of ventilation
number of days participant receive ventilatory support
Measured: Participants will be assessed from the date of randomization up to 28 days of life or date of death from any cause, whichever came first.
Weight change (gain/loss)
daily weight gain or loss of the participants in grams (g)
Measured: Participants will be assessed for daily weight from the date of randomization up to 28 days of life or date of death from any cause, whichever came first.
use of inotropes, plasma volume expanders and sodium bicarbonate therapy
total number of days participants required inotropic support
Measured: Participants will be assessed for the use of inotropes, plasma volume expanders and sodium bicarbonate therapy from the date of randomization up to 28 days of life or date of death from any cause, whichever came first.
survival
participant survival or death
Measured: up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2024
- Study start10 Jul 2024
- Primary completion10 May 2025 (estimated)
- Study completion10 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic AcidosisStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Infants who will meet the inclusion criteria and whose parents will consent to participate will be randomized to one of the two intervention groups (So-A, or the standard So-C) prior to the preparation and commencement of PN. Randomization will be performed by pharmacists at the Sterile Preparation/Parenteral Unit of AKU hospital upon enrolment of each case. The randomization process will be performed according to a computer-generated list. For multiple births, each infant will be individually randomized. The interventional group: This group will receive sodium acetate in the neonatal PN. Control Group: The control group will receive sodium chloride in the neonatal PN. Intervention of the study: Use of sodium acetate in neonatal PN.
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aga Khan University Hospital, Pakistan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adnan Mirza, Aga Khan University Hospital, Pakistan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06545565
- Sponsor's protocol ID
- 2024-6523-29448
- Acronym
- PROTECT
- Status last verified
- Aug 2024
- First submitted
- 30 Jul 2024
- Last updated
- 9 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Metabolic Acidosis in Preterm Neonates by Replacing Sodium Chloride With Sodium Acetate in Parenteral Nutrition - A Randomized Controlled Trial. (PROTECT Trial)
- ClinicalTrials.gov ID
- NCT06545565
- Acronym / sponsor ID
- PROTECT / 2024-6523-29448
- Conditions
- Metabolic Acidosis, Neonatal Disease, Neonatal Complication
- Keywords
- metabolic acidosis, sodium acetate, neonates, Parenteral Nutrition
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Aga Khan University Hospital, PakistanUniversity, hospital or other
- Study start
- 10 Jul 2024 (actual)
- Primary completion
- 10 May 2025 (estimated)
- Study completion
- 10 May 2025 (estimated)
- First posted
- 9 Aug 2024 (actual)
- 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 goal of this clinical trial is to learn if the addition of sodium acetate in neonatal PN works to prevent and treat metabolic acidosis and associated comorbidities in preterm neonates. It will also teach about the optimal doses of sodium acetate in PN. The main questions it aims to answer are:
Is the incidence of metabolic acidosis reduced in preterm neonates who received daily Sodium acetate in PN therapy (treatment) during the initial weeks of life compared with individuals who received sodium chloride in PN (standard)? Is the rate of neonatal comorbidities reduced in preterm neonates who received daily Sodium acetate in PN therapy (treatment) during the initial weeks of life compared with individuals who received sodium chloride in PN (standard)? What are the optimal neonatal dosing recommendations/guidelines of sodium acetate in daily PN, which are required to prevent/treat metabolic acidosis in the early life of preterm neonates? Researchers will compare Sodium acetate in PN therapy to sodium chloride in PN to see if Sodium acetate works to prevent and treat metabolic acidosis and associated comorbidities.
Included Participants:
All the neonates were admitted to the NICU of AKUH and received PN during 28 days of their lives.
Participants will receive sodium acetate or sodium chloride Written informed consent was obtained by parents/legal representatives (according to local regulations) before the initiation of PN. Gestational age < 33 weeks Included in the study before 72 hours of life
Detailed description
Background Providing optimal nutritional support to extremely preterm and very low birth weight (VLBW) infants is still very much a challenge, as enteral feeding is generally delayed due to the prematurity of gastrointestinal function; these infants have poor sucking and swallowing reflexes, and there are concerns that a liberal feeding strategy may lead to complications, such as feeding intolerance or necrotizing enterocolitis (NEC). Early nutritional support is primarily delivered through parenteral nutrition (PN) is essential in the critical management during the neonatal period in these preterm babies.
PN provides all the required nutritional needs of preterm, including fluid, calories, and electrolytes. Sodium is both an electrolyte and a mineral. It helps keep the water (the amount of fluid inside and outside the body's cells) and electrolyte balance of the body. Sodium is also important in how nerves and muscles work. Most of the sodium in the body (about 85%) is found in blood and lymph fluid. Sodium is also provided through PN in two forms The first form is sodium chloride. In most parts of the world, sodium supplementation in PN has largely been in the form of sodium chloride. This is also the standard of care in the neonatal intensive care unit of Aga Khan University Hospital. Sodium chloride is added to the PN according to the sodium levels and body fluid balance.
The second source of sodium is sodium acetate, which is new in Aga Khan University Hospital but internationally used in PN. Daily sodium acetate will be added to the PN bag according to the sodium levels, acid-base balance, and total fluid intake. With the addition of sodium acetate, neonates have fewer metabolic acidosis complications, are more effective in preventing comorbidities, and are being used in the NICUs of developed countries.
MATERIALS AND METHODS Design This will be a 2-arm open-label phase III randomized controlled trial (RCT) to compare Sodium acetate and Sodium chloride, given daily as the component of parenteral nutrition over during first 28 days of life. Investigators will initiate the treatment within the first 72 hours following birth.
Setting This study will be conducted in the Neonatal Intensive Care Unit (NICU) of the Aga Khan University Hospital (AKUH), which is a 700-bedded, not-for-profit tertiary care hospital receiving country-wide referrals.
The interventional group: This group will receive sodium acetate in the neonatal PN.
Control Group: The control group will receive sodium chloride in the neonatal PN.
Intervention of the study: Use of sodium acetate in neonatal PN.
Data collection:
All relevant maternal and infant demographic data/Baseline characteristics, blood investigation results, and clinical outcomes will be recorded prospectively. The primary outcomes, pH, and base excess (BE) will be recorded from pre-PN on the first day of life (DOL), then 2- 7 DOL, and days 10, 13, 16,20,25, and 28 of life. For infants requiring less than 28 days of hospital stay, data will be collected till discharge/death.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Infants who will meet the inclusion criteria and whose parents will consent to participate will be randomized to one of the two intervention groups (So-A, or the standard So-C) prior to the preparation and commencement of PN. Randomization will be performed by pharmacists at the Sterile Preparation/Parenteral Unit of AKU hospital upon enrolment of each case. The randomization process will be performed according to a computer-generated list. For multiple births, each infant will be individually randomized. The interventional group: This group will receive sodium acetate in the neonatal PN. Control Group: The control group will receive sodium chloride in the neonatal PN. Intervention of the study: Use of sodium acetate in neonatal PN.
| Arm | Type | Receives |
|---|---|---|
| sodium acetate | Experimental | Drug: sodium acetate group will receive sodium acetate in the neonatal PN. |
| Sodium Chloride | Active comparator | Drug: sodium chloride group will receive sodium chloride in the neonatal PN. |
Who may qualify
- Ages
- 1 day to 3 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Written informed consent obtained by parents/legal representative (according to local regulations) before the initiation of PN.
- All the neonates who were admitted to the NICU of AKUH and received PN during 28 days of their life.
- Gestational age < 33 weeks
Key exclusion criteria (6 listed)
- Infants with an inborn error of metabolism
- Genetic or congenital condition that affects neurodevelopment or requires multiple surgeries (e.g., congenital viral infection, hydrops, complex congenital heart disease, severe dysmorphic features, etc.)
- Severe metabolic alkalosis, in critically ill neonates, is defined as a persistent elevation of the serum pH above 7.45 and it also involves a primary increase in serum bicarbonate (HCO3-) concentration > 25mEq/L.
- Severe Hypernatremia, in critically ill neonates, is defined as persistently high serum sodium levels > 150 mmol/L
- Severe liver failure and syndromic infants with multiple congenital abnormalities and severe perinatal asphyxia
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 |
|---|---|---|
| sodium acetate group will receive sodium acetate in the neonatal PN.Also: Sodium AcetateThis group will receive sterile sodium acetate daily in the neonatal PN for the duration the patient will receive parenteral nutrition, a maximum of 28 days of life. | Drug | sodium acetate |
| sodium chloride group will receive sodium chloride in the neonatal PN.Also: sodium ChlorideThis group will receive sterile sodium chloride daily in the neonatal PN for the duration the patient will receive parenteral nutrition, a maximum of 28 days of life. | Drug | Sodium Chloride |
Primary outcome
metabolic acidosis
Time frame: Blood-ph and serum-bicarbonate concentration will be recorded from pre-PN on the first day of life (DOL), then 2-7 DOL, and days 10,13,16,20,25&28 of life. For infants requiring <28 days of hospital stay until discharge/death.
Severe metabolic acidosis, in critically ill neonates, is defined as a persistent low Blood pH < 7.26 and it also involves a primary decrease in serum bicarbonate (HCO3-) concentration <16 mEq/L]
5 secondary outcomes
Development of Comorbid conditions (Bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), Intraventricular hemorrhage (IVH), Retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), Sepsis and jaundice ).
Time frame: From the date of randomization until the date of first documented comorbid condition, assessed up to 28 days of life or date of death from any cause, whichever came first.
Duration of ventilation
Time frame: Participants will be assessed from the date of randomization up to 28 days of life or date of death from any cause, whichever came first.
Weight change (gain/loss)
Time frame: Participants will be assessed for daily weight from the date of randomization up to 28 days of life or date of death from any cause, whichever came first.
use of inotropes, plasma volume expanders and sodium bicarbonate therapy
Time frame: Participants will be assessed for the use of inotropes, plasma volume expanders and sodium bicarbonate therapy from the date of randomization up to 28 days of life or date of death from any cause, whichever came first.
survival
Time frame: up to 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- 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.
Adnan Mirza, MBBS contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing sodium acetate group will receive sodium acetate in the neonatal PN. and sodium chloride group will receive sodium chloride in the neonatal PN. in people with Metabolic Acidosis and Neonatal Disease, run by Aga Khan University Hospital, Pakistan at 1 site in Pakistan.
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 3 inclusion and 6 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 9 Aug 2024. 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 Pakistan. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Gul Ambreen, PhD (+92 3002402035, gul.ambreen@aku.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
metabolic acidosis (time frame: Blood-ph and serum-bicarbonate concentration will be recorded from pre-PN on the first day of life (DOL), then 2-7 DOL, and days 10,13,16,20,25&28 of life. For infants requiring <28 days of hospital stay until discharge/death.). 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 9 Aug 2024.