Hand, Foot and Mouth DiseasePhase 2NCT01940250
Magnesium Sulphate for Severe Hand, Foot and Mouth Disease in Vietnam
A Phase 2 study testing Magnesium Sulphate and Sterile water in people with Hand, Foot and Mouth Disease, run by Oxford University Clinical Research Unit, Vietnam at 2 sites in Vietnam.
Trial summary
Hand foot and mouth disease (HFMD) is a common infectious disease caused by a number of different viruses - a small proportion of children infected with a particular type of enterovirus (EV71) develop neurological and systemic complications that may prove fatal. Read more about this study
- Who is it for?
- Ages 6 months to 15 years
- Conditions the study is for
- Hand, Foot and Mouth Disease
- What is being tested?
- Magnesium Sulphate and Sterile water
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 2 sitesVietnam
- Study dates
- 21 Apr 2014to 28 Dec 2016
- Phase
- Phase 2
- 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 6 months to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 6 months to 15 years
- Clinical suspicion of HFMD requiring PICU/HDU admission
- Considered severe enough to warrant invasive blood pressure monitoring by PICU/HDU staff
- Development of hypertension defined as follows:
- For children aged 1 year and over, at least 3 consecutive systolic blood pressure recordings above the 95th centile for age, gender and length (USA guidelines for defining Stage 1 hypertension in children, (Appendix 2)) measured invasively over a period of 20 minutes provided the child is not distressed or crying [30, 31].
- For children aged 6 months to 1 year, systolic BP > 100 mm Hg measured invasively on at least 3 occasions over a period for 20 minutes provided the child is not distressed or crying
Show all 15Show fewer
- Plus one or more of the following criteria:
- Tachypnoea for age
- Irregular or labored breathing, but with SpO2 above 92% in air and normal ABG (pH, pCO2, pO2, HCO3 all within the normal range for the local laboratory)
- Resting heart rate > 150 bpm
- Mottled skin
- Profuse sweating
- Refractory fever
- Hyperglycemia
- Informed consent
Who cannot join
- Past history of hypertension, chronic renal, cardiac or pulmonary disease, or any neurological disorder
- Hypertensive emergency
- Already commenced milrinone or any other inotropic agents
- Respiratory distress with SpO2<92% in air or PaCO2>45 mm Hg
- AV block or any arrhythmia
- Acute renal failure
Trial locations and contacts
2 sites in 1 country.
Vietnam2 sites
Children's Hospital 1
Ho Chi Minh City
Hospital for Tropical Diseases
Ho Chi Minh City
About this study
Official title: A Randomized, Placebo-controlled, Double-blind Trial of Intravenous Magnesium Sulfate for the Management of Severe Hand, Foot and Mouth Disease With Autonomic Nervous System Dysregulation in Vietnamese Children.
Hand foot and mouth disease (HFMD) is a common infectious disease caused by a number of different viruses - a small proportion of children infected with a particular type of enterovirus (EV71) develop neurological and systemic complications that may prove fatal. Very large epidemics of EV71 related HFMD have occurred across Asia in recent years; in 2011, in excess of 100,000 Vietnamese children were diagnosed with HFMD and 164 died.
In children with severe HFMD the particular part of the brain that regulates the heart, blood circulation, and breathing responses can be affected. Management of this complication is very difficult and we currently use an expensive drug (milrinone) that is hard to obtain and has significant side effects, without having good evidence that it is effective.
Read more
Magnesium sulphate (Mg) is a cheap, readily available drug that has been used in other diseases with similar complications, and we have preliminary data from a small case series that suggests it might be a good treatment for HFMD patients with signs indicating this type of brain involvement.
We think that early intervention with Mg, when signs of brain involvement are still relatively mild, will control this problem better than waiting until it is well established and giving milrinone as at present, and this in turn may prevent progression to severe disease. The aims of the project are to evaluate the effects of Mg on hypertension, signs of brain dysfunction, outcome (death or neurological sequelae), changes in a variety of blood and urine components, and measures of cardiovascular function, in severe HFMD.
The study design is a randomized double-blind placebo-controlled clinical trial. Children on the pediatric intensive care unit with a clinical diagnosis of hand, foot and mouth disease will be eligible for enrolment if the blood pressure exceeds the internationally recognized threshold for Stage 1 hypertension, they exhibit at least one other sign of brain stem dysfunction, and there is written informed consent by a parent or guardian.
According to the randomization, patients will receive an initial loading dose followed by a maintenance infusion, of either Mg or identical placebo for 72 hours; all staff involved in patient care will remain unaware of the treatment allocation, but staff from another department will monitor Mg blood levels to ensure safety and adequate dosing. A total of 190 patients (95 in each arm) will be recruited.
Read the detailed description
Background:
Hand foot and mouth disease (HFMD) is a common infectious disease caused by a variety of enteroviruses. A small proportion of those infected with enterovirus 71 (EV71) develop neurological and systemic complications that may prove fatal. Over the past 15 years EV71 related HFMD has caused increasing epidemics of HFMD across Asia; in 2011, in excess of 100,000 Vietnamese children were diagnosed clinically with HFMD and 164 died. The neurological problem of most concern is brainstem encephalitis, causing autonomic nervous system (ANS) dysregulation that may progress rapidly to cardiopulmonary failure. Management of ANS dysregulation is difficult even in sophisticated western intensive care units. The phosphodiesterase-3 inhibitor, Milrinone, was reported to control hypertension and support myocardial function in a small informal study of severe HFMD compared to historical controls, but in practice treatment remains largely empirical. ANS dysregulation also occurs in severe tetanus and there is a body of evidence indicating that intravenous magnesium sulphate (Mg) is effective in controlling tetanus-associated cardiovascular instability. Mg is also used widely for eclampsia, severe asthma and pulmonary hypertension, and there are reports of rapid control of life-threatening autonomic hyperreflexia in patients with spinal lesions. Formal safety data in children are limited, but adverse effects appear to be infrequent. In a series of 24 severe EV71 confirmed HFMD cases managed recently at the Hospital for Tropical Diseases, Ho Chi Minh City, Mg was added when hypertension remained poorly controlled despite high-dose Milrinone. In all cases the blood pressure (BP) reduced within 30-60 minutes and remained stable subsequently on a continuous Mg infusion for 48-72 hours.
Hypothesis and Aims:
We hypothesize that early intervention with Mg, when ANS dysregulation first becomes apparent, will control cardiovascular instability and prevent progression to severe disease. The main aims are as follows:-
- To evaluate the effects of Mg on hypertension and ANS dysregulation in severe HFMD
- To evaluate the effects of Mg on outcome (death or neurological sequelae) in severe HFMD
- To evaluate changes in plasma/urine catecholamine levels, cardiac output and systemic vascular resistance (SRV) in severe HFMD, and to assess the impact of Mg on these parameters.
Study Design:
We plan a randomized double blind trial comparing intravenous Mg with placebo in children admitted to the pediatric intensive care unit with clinical HFMD, ANS dysregulation, and Stage 1 hypertension. Patients will be eligible for enrolment if the arterial blood pressure exceeds the 95th centile for age, gender and length/height for at least 30 minutes while the child is not distressed, they exhibit at least one other criterion for ANS dysregulation, and a parent/guardian gives written informed consent. Specific renal and cardio-respiratory exclusion criteria will apply.
A loading dose of 50mg/kg of either Mg or identical placebo will be given over 20 minutes followed by a maintenance infusion for 72 hours according to response, aiming for Mg levels 2-3 times normal in the treatment arm. All staff involved in clinical care will be blind to the treatment allocation, and Mg levels will be monitored and adjusted by independent doctors from another clinical facility.
The primary endpoint will be a composite endpoint of disease progression defined as occurrence of any of the following within 72 hours: specific blood pressure criteria necessitating addition of milrinone, need for ventilation, development of shock, or death. Secondary endpoints will include presence of neurological sequelae at discharge in survivors, and various measures of cardiac output and systemic vascular resistance, catecholamine and cytokine levels.
Based on 1:1 randomization, an anticipated relative reduction of the risk of progression of 50% (from 50% in the control arm to 25% in Mg recipients, information from our case series plus indirect evidence from studies on severe tetanus), 90% power and a two-sided 5% significance level, 85 patients per treatment group are required. To allow for some violations of our assumptions and losses to follow-up, we plan to recruit 190 patients (95 patients per treatment arm) into the study.
Potential Impact:
Given the very large numbers of HFMD cases being seen in hospitals in Asia currently, if Mg is shown to be effective in controlling ANS dysregulation and preventing severe HFMD complications this would be of major importance for paediatric care throughout the Asian region. Mg is cheap, readily available and safe whereas milrinone is expensive, has a significant side effect profile and is often not available outside major centres.
- Conditions
- Hand, Foot and Mouth Disease
- Being tested
- Magnesium Sulphate, Sterile water
- Keywords
- Hand, foot and mouth disease, Autonomic nervous system dysregulation, Magnesium sulphate
- Medical subject headings
- Hand, Foot and Mouth Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnesium SulphateDrug
Also called magnesi sulfat krabi 15%
MgSO4 IV infusion
Sterile waterDrug
H2O IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Sterile water | Placebo comparator | Sterile water will be packaged identically to the active comparator.
Each patient randomized to the placebo arm of the trial will receive a loading dose of 0.5ml/kg intravenous over 20 minutes , followed by a maintenance dose of 0.3 ml/kg/hr to 0.5 ml/kg/hr randomly adjusted by an independent doctor to mimic adjustments made in the active comparator arm for 72 hrs. Receives: Drug: Sterile water |
| Magnesium sulphate | Active comparator | Each patient randomized to the treatment arm of the trial will receive a loading dose of 50mg/kg intravenous over 20 minutes (0.5ml/kg), followed by a maintenance dose of 30-50 mg/kg/hr (0.3 ml/kg/hr to 0.5 ml/kg/hr) for 72 hrs.
The maintenance dose will be determined by increasing the loading infusion dose 0.1 ml/kg/hr (10mg/kg/hr) every 15 minutes to a maximum dose of 0.5 ml/kg/hr (50 mg/kg/hr), with the following caveats:
* If the systolic BP decreases to < 90th percentile for age, gender and length the dose will be reduced by 1 stage every 15 mins
* If the systolic BP increases to the levels detailed in the study protocol for treatment failure, action will be taken as indicated
* If the systolic BP decrease rapidly more than 25% over 15 minutes
* If the plasma Mg level > 2.5 mmol/l or < 1.8 mmol/l a 25% increase or decrease in the infusion rate will be implemented as appropriate. Receives: Drug: Magnesium Sulphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients who experience at least one of the clinical events listed below (composite endpoint)
Number of patients who meet one or more of the following criteria:
- Blood pressure criteria necessitating addition of milrinone following Vietnam Ministry of Health guidelines for the treatment of hand, foot and mouth disease
- Need for mechanical ventilation
- Development of shock
- Death
Measured: 72 hours after start of study drug infusion
Secondary outcomes (9)
Death
Measured: 72 hours after start of study drug infusion
Blood pressure criteria necessitating addition of milrinone following Vietnam Ministry of Health guidelines for the treatment of hand, foot and mouth disease
Measured: 72 hours after start of study drug infusion
Need for mechanical ventilation
According to Viet Nam Ministry of Health guidelines: Ventilation Criteria:
If a patient continues to display any of the following criteria despite oxygenation via nasal cannula and cardiac support with inotropic drugs for more than 60 minutes.
- Labored breathing
- Tachypnea with resting respiratory rate > 70 / minute without fever
- Hypoxemia and/or fluctuating SpO2
- Poor tissue perfusion and persistent resting heart rate > 180 beats/minute without fever
Or
- Decorticate or decerebrate rigidity
- Coma (Glasgow Coma Scale < 10 )
Measured: 72 hours after start of study drug infusion
Development of shock
Measured: 72 hours after start of study drug infusion
Requirement for inotropic agents (eg dobutamine)
If heart rate> 170 beats/minute
Measured: During hospital admission - expected average length of admission 5 days
Presence of neurological sequelae at discharge in survivors
Number of surviving patients who have neurological sequelae at hospital discharge
Measured: At hospital discharge - expected average discharge day 5
Neurodevelopmental status
Measured by . Children 36 months and under at enrollment will use the Bayley infant scales of development III. Children 48 months and above at enrollment will use the Movement ABC-2 tool for their assessments. The children aged between 37 and 47 months at enrolment will have both assessments done at both visits.
Measured: 6 months
Duration of hospitalization
Number of days from study enrollment to discharge
Measured: At hospital discharge - expected average discharge day 5
Number of adverse events and serious adverse events
Number of adverse events and severe adverse events that occur in the two treatment arms during hospitalization.
Measured: During hospital admission - expected average length of admission 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2013 (estimated)
- Study start21 Apr 2014
- Primary completion30 Jun 2016
- Study completion28 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hand, Foot and Mouth DiseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oxford University Clinical Research Unit, Vietnam
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Children's Hospital Number 1, Ho Chi Minh City, Vietnam
- Responsible party
- Sponsor
- Investigators
- Bridget Wills, MD, Principal investigator, Oxford University Clinical Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01940250
- Sponsor's protocol ID
- 02EI
- Status last verified
- Nov 2014
- First submitted
- 22 Aug 2013
- Last updated
- 7 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Phan QT, Phung LK, Truong KH, Huynh TT, Pham GT, Nguyen BN, Tran QT, Huynh VNT, Nguyen TTM, Le TPK, Le NNT, Sabanathan S, van Doorn HR, Van Le T, Nguyen TD, Merson L, Nguyen DTP, Geskus R, Nguyen HT, Nguyen CVV, Wills B. Assessing the efficacy and safety of magnesium sulfate for management of autonomic nervous system dysregulation in Vietnamese children with severe hand foot and mouth disease. BMC Infect Dis. 2019 Aug 22;19(1):737. doi: 10.1186/s12879-019-4356-x.
PubMed 31438878Qui PT, Khanh TH, Trieu HT, Giang PT, Bich NN, Thoa le PK, Nhan le NT, Sabanathan S, Van Doorn R, Toan ND, Merson L, Dung NT, Khanh LP, Wolbers M, Hung NT, Chau NV, Wills B. Intravenous magnesium sulfate for the management of severe hand, foot, and mouth disease with autonomic nervous system dysregulation in Vietnamese children: study protocol for a randomized controlled trial. Trials. 2016 Feb 19;17:98. doi: 10.1186/s13063-016-1215-6.
PubMed 26896318
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Double-blind Trial of Intravenous Magnesium Sulfate for the Management of Severe Hand, Foot and Mouth Disease With Autonomic Nervous System Dysregulation in Vietnamese Children.
- ClinicalTrials.gov ID
- NCT01940250
- Acronym / sponsor ID
- 02EI
- Conditions
- Hand, Foot and Mouth Disease
- Keywords
- Hand, foot and mouth disease, Autonomic nervous system dysregulation, Magnesium sulphate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Oxford University Clinical Research Unit, VietnamUniversity, hospital or other
- Collaborators
- Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Children's Hospital Number 1, Ho Chi Minh City, Vietnam
- Study start
- 21 Apr 2014 (actual)
- Primary completion
- 30 Jun 2016 (actual)
- Study completion
- 28 Dec 2016 (actual)
- First posted
- 12 Sep 2013 (estimated)
- 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.
Hand foot and mouth disease (HFMD) is a common infectious disease caused by a number of different viruses - a small proportion of children infected with a particular type of enterovirus (EV71) develop neurological and systemic complications that may prove fatal. Very large epidemics of EV71 related HFMD have occurred across Asia in recent years; in 2011, in excess of 100,000 Vietnamese children were diagnosed with HFMD and 164 died.
In children with severe HFMD the particular part of the brain that regulates the heart, blood circulation, and breathing responses can be affected. Management of this complication is very difficult and we currently use an expensive drug (milrinone) that is hard to obtain and has significant side effects, without having good evidence that it is effective.
Magnesium sulphate (Mg) is a cheap, readily available drug that has been used in other diseases with similar complications, and we have preliminary data from a small case series that suggests it might be a good treatment for HFMD patients with signs indicating this type of brain involvement.
We think that early intervention with Mg, when signs of brain involvement are still relatively mild, will control this problem better than waiting until it is well established and giving milrinone as at present, and this in turn may prevent progression to severe disease. The aims of the project are to evaluate the effects of Mg on hypertension, signs of brain dysfunction, outcome (death or neurological sequelae), changes in a variety of blood and urine components, and measures of cardiovascular function, in severe HFMD.
The study design is a randomized double-blind placebo-controlled clinical trial. Children on the pediatric intensive care unit with a clinical diagnosis of hand, foot and mouth disease will be eligible for enrolment if the blood pressure exceeds the internationally recognized threshold for Stage 1 hypertension, they exhibit at least one other sign of brain stem dysfunction, and there is written informed consent by a parent or guardian.
According to the randomization, patients will receive an initial loading dose followed by a maintenance infusion, of either Mg or identical placebo for 72 hours; all staff involved in patient care will remain unaware of the treatment allocation, but staff from another department will monitor Mg blood levels to ensure safety and adequate dosing. A total of 190 patients (95 in each arm) will be recruited.
Detailed description
Background:
Hand foot and mouth disease (HFMD) is a common infectious disease caused by a variety of enteroviruses. A small proportion of those infected with enterovirus 71 (EV71) develop neurological and systemic complications that may prove fatal. Over the past 15 years EV71 related HFMD has caused increasing epidemics of HFMD across Asia; in 2011, in excess of 100,000 Vietnamese children were diagnosed clinically with HFMD and 164 died. The neurological problem of most concern is brainstem encephalitis, causing autonomic nervous system (ANS) dysregulation that may progress rapidly to cardiopulmonary failure. Management of ANS dysregulation is difficult even in sophisticated western intensive care units. The phosphodiesterase-3 inhibitor, Milrinone, was reported to control hypertension and support myocardial function in a small informal study of severe HFMD compared to historical controls, but in practice treatment remains largely empirical. ANS dysregulation also occurs in severe tetanus and there is a body of evidence indicating that intravenous magnesium sulphate (Mg) is effective in controlling tetanus-associated cardiovascular instability. Mg is also used widely for eclampsia, severe asthma and pulmonary hypertension, and there are reports of rapid control of life-threatening autonomic hyperreflexia in patients with spinal lesions. Formal safety data in children are limited, but adverse effects appear to be infrequent. In a series of 24 severe EV71 confirmed HFMD cases managed recently at the Hospital for Tropical Diseases, Ho Chi Minh City, Mg was added when hypertension remained poorly controlled despite high-dose Milrinone. In all cases the blood pressure (BP) reduced within 30-60 minutes and remained stable subsequently on a continuous Mg infusion for 48-72 hours.
Hypothesis and Aims:
We hypothesize that early intervention with Mg, when ANS dysregulation first becomes apparent, will control cardiovascular instability and prevent progression to severe disease. The main aims are as follows:-
- To evaluate the effects of Mg on hypertension and ANS dysregulation in severe HFMD
- To evaluate the effects of Mg on outcome (death or neurological sequelae) in severe HFMD
- To evaluate changes in plasma/urine catecholamine levels, cardiac output and systemic vascular resistance (SRV) in severe HFMD, and to assess the impact of Mg on these parameters.
Study Design:
We plan a randomized double blind trial comparing intravenous Mg with placebo in children admitted to the pediatric intensive care unit with clinical HFMD, ANS dysregulation, and Stage 1 hypertension. Patients will be eligible for enrolment if the arterial blood pressure exceeds the 95th centile for age, gender and length/height for at least 30 minutes while the child is not distressed, they exhibit at least one other criterion for ANS dysregulation, and a parent/guardian gives written informed consent. Specific renal and cardio-respiratory exclusion criteria will apply.
A loading dose of 50mg/kg of either Mg or identical placebo will be given over 20 minutes followed by a maintenance infusion for 72 hours according to response, aiming for Mg levels 2-3 times normal in the treatment arm. All staff involved in clinical care will be blind to the treatment allocation, and Mg levels will be monitored and adjusted by independent doctors from another clinical facility.
The primary endpoint will be a composite endpoint of disease progression defined as occurrence of any of the following within 72 hours: specific blood pressure criteria necessitating addition of milrinone, need for ventilation, development of shock, or death. Secondary endpoints will include presence of neurological sequelae at discharge in survivors, and various measures of cardiac output and systemic vascular resistance, catecholamine and cytokine levels.
Based on 1:1 randomization, an anticipated relative reduction of the risk of progression of 50% (from 50% in the control arm to 25% in Mg recipients, information from our case series plus indirect evidence from studies on severe tetanus), 90% power and a two-sided 5% significance level, 85 patients per treatment group are required. To allow for some violations of our assumptions and losses to follow-up, we plan to recruit 190 patients (95 patients per treatment arm) into the study.
Potential Impact:
Given the very large numbers of HFMD cases being seen in hospitals in Asia currently, if Mg is shown to be effective in controlling ANS dysregulation and preventing severe HFMD complications this would be of major importance for paediatric care throughout the Asian region. Mg is cheap, readily available and safe whereas milrinone is expensive, has a significant side effect profile and is often not available outside major centres.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sterile water | Placebo comparator | Drug: Sterile waterSterile water will be packaged identically to the active comparator. Each patient randomized to the placebo arm of the trial will receive a loading dose of 0.5ml/kg intravenous over 20 minutes , followed by a maintenance dose of 0.3 ml/kg/hr to 0.5 ml/kg/hr randomly adjusted by an independent doctor to mimic adjustments made in the active comparator arm for 72 hrs. |
| Magnesium sulphate | Active comparator | Drug: Magnesium SulphateEach patient randomized to the treatment arm of the trial will receive a loading dose of 50mg/kg intravenous over 20 minutes (0.5ml/kg), followed by a maintenance dose of 30-50 mg/kg/hr (0.3 ml/kg/hr to 0.5 ml/kg/hr) for 72 hrs. The maintenance dose will be determined by increasing the loading infusion dose 0.1 ml/kg/hr (10mg/kg/hr) every 15 minutes to a maximum dose of 0.5 ml/kg/hr (50 mg/kg/hr), with the following caveats: * If the systolic BP decreases to < 90th percentile for age, gender and length the dose will be reduced by 1 stage every 15 mins * If the systolic BP increases to the levels detailed in the study protocol for treatment failure, action will be taken as indicated * If the systolic BP decrease rapidly more than 25% over 15 minutes * If the plasma Mg level > 2.5 mmol/l or < 1.8 mmol/l a 25% increase or decrease in the infusion rate will be implemented as appropriate. |
Who may qualify
- Ages
- 6 months to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (15 listed)
- Age 6 months to 15 years
- Clinical suspicion of HFMD requiring PICU/HDU admission
- Considered severe enough to warrant invasive blood pressure monitoring by PICU/HDU staff
- Development of hypertension defined as follows:
- Plus one or more of the following criteria:
Key exclusion criteria (6 listed)
- Past history of hypertension, chronic renal, cardiac or pulmonary disease, or any neurological disorder
- Hypertensive emergency
- Already commenced milrinone or any other inotropic agents
- Respiratory distress with SpO2<92% in air or PaCO2>45 mm Hg
- AV block or any arrhythmia
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 |
|---|---|---|
| Magnesium SulphateAlso: magnesi sulfat krabi 15%MgSO4 IV infusion | Drug | Magnesium sulphate |
| Sterile waterH2O IV infusion | Drug | Sterile water |
Primary outcome
Number of patients who experience at least one of the clinical events listed below (composite endpoint)
Time frame: 72 hours after start of study drug infusion
Number of patients who meet one or more of the following criteria: 1. Blood pressure criteria necessitating addition of milrinone following Vietnam Ministry of Health guidelines for the treatment of hand, foot and mouth disease 2. Need for mechanical ventilation 3. Development of shock 4. Death
9 secondary outcomes
Death
Time frame: 72 hours after start of study drug infusion
Blood pressure criteria necessitating addition of milrinone following Vietnam Ministry of Health guidelines for the treatment of hand, foot and mouth disease
Time frame: 72 hours after start of study drug infusion
Need for mechanical ventilation
Time frame: 72 hours after start of study drug infusion
Development of shock
Time frame: 72 hours after start of study drug infusion
Requirement for inotropic agents (eg dobutamine)
Time frame: During hospital admission - expected average length of admission 5 days
Presence of neurological sequelae at discharge in survivors
Time frame: At hospital discharge - expected average discharge day 5
Neurodevelopmental status
Time frame: 6 months
Duration of hospitalization
Time frame: At hospital discharge - expected average discharge day 5
Number of adverse events and serious adverse events
Time frame: During hospital admission - expected average length of admission 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
- Derived from this study: PubMed 31438878Phan QT, Phung LK, Truong KH, Huynh TT, Pham GT, Nguyen BN, Tran QT, Huynh VNT, Nguyen TTM, Le TPK, Le NNT, Sabanathan S, van Doorn HR, Van Le T, Nguyen TD, Merson L, Nguyen DTP, Geskus R, Nguyen HT, Nguyen CVV, Wills B. Assessing the efficacy and safety of magnesium sulfate for management of autonomic nervous system dysregulation in Vietnamese children with severe hand foot and mouth disease. BMC Infect Dis. 2019 Aug 22;19(1):737. doi: 10.1186/s12879-019-4356-x.
- Derived from this study: PubMed 26896318Qui PT, Khanh TH, Trieu HT, Giang PT, Bich NN, Thoa le PK, Nhan le NT, Sabanathan S, Van Doorn R, Toan ND, Merson L, Dung NT, Khanh LP, Wolbers M, Hung NT, Chau NV, Wills B. Intravenous magnesium sulfate for the management of severe hand, foot, and mouth disease with autonomic nervous system dysregulation in Vietnamese children: study protocol for a randomized controlled trial. Trials. 2016 Feb 19;17:98. doi: 10.1186/s13063-016-1215-6.
- Oxford University Clinical Research Unit, Viet NamLink provided by the sponsor.
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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.
Bridget Wills, MD principal investigator
Oxford University Clinical Research Unit
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Magnesium Sulphate and Sterile water in people with Hand, Foot and Mouth Disease, run by Oxford University Clinical Research Unit, Vietnam at 2 sites in Vietnam.
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 15 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: finished, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Vietnam. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients who experience at least one of the clinical events listed below (composite endpoint) (time frame: 72 hours after start of study drug infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01940250, which also lists 2 linked publications.
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 7 Mar 2017.