PIPSICKLE TRIAL: The journey so far

PIPSICKLE TRIAL: The journey so far

Prof. Bosede B. Afolabi (Principal Investigator)
Department of Obstetrics & Gynaecology,
College of Medicine, University of Lagos / Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria

What is PIPSICKLE Trial?

PIPSICKLE is an acronym, which stands for “Preventing Intrauterine growth restriction and Pre-eclampsia in Sickle cell pregnancy”.  It is a randomized controlled trial funded by the Tertiary Education Trust Fund (TETFund), Nigeria.  The study is geared towards discovering additional preventive strategies to minimize the risk of some complications such as intrauterine growth restriction (baby not attaining its full growth potential), stillbirths, miscarriages, preeclampsia (a pregnancy related disorder characterized by high blood pressure), amongst others, in pregnant women with sickle cell disorder.

Why PIPSICKLE Trial?

Pregnancy in women with sickle cell disorder is associated with many complications including preeclampsia (PE) and intrauterine growth restriction (IUGR).  With the recent advancement in medical technology worldwide, more women with sickle cell disorder are successfully growing into adulthood and getting pregnant despite the higher risk of complications (1, 2, 3).  Therefore, there is a need to improve the quality of medical care they receive during pregnancy and delivery.

In our earlier research work, we found that there is an abnormality in the ratio of certain biochemical substances (prostacyclin and thromboxane) in the blood of pregnant women with sickle cell disorder (4), like what has been found in pregnant women without sickle cell disorder who develop complications like preeclampsia and unexplained intrauterine growth restriction (5).

Fortunately, low dose aspirin has been found to be effective in reversing this abnormality in pregnant women who do not have sickle cell disorder (6).  We have been using low dose aspirin in pregnancy for certain indications and it is generally known to be safe in pregnancy (7) and is recommended in obstetric guidelines for this use in preventing intrauterine growth restriction and preeclampsia.  It has also been suggested for use in sickle cell pregnancy (8) but, unfortunately, it has not been tested in them even though women with this disorder are at a higher risk for these complications.

This trial will determine if low dose aspirin offers significant benefit in reducing the occurrence of these complications if given routinely to pregnant women with sickle cell disorder.

Who qualifies for the PIPSICKLE Trial?

If your Genotype is SS or SC and you are between 12 to 28 weeks (i.e., between 3 to 6⅟₂ months) pregnant, you qualify for the trial.  You also must meet other selection criteria on assessment.  We are recruiting 476 pregnant women who have sickle cell disorder for this research.

This research commenced on 1^st July 2020.  The trial will remain open until we get the number of pregnant women with sickle cell disorder that we need.

Where can I go to in order to participate in the Trial?

The coordinating centre for this trial is the Department of Obstetrics and Gynaecology, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria because the research is being funded by the Federal Government of Nigeria through the University of Lagos.  All intending participants can register for Antenatal Care at any of the 15 selected hospitals across and outside Lagos State closest to them viz:

1. Lagos University Teaching Hospital (LUTH), Idi-Araba, Lagos State
2. Lagos State University Teaching Hospital (LASUTH), Ikeja, Lagos State
3. Alimosho General Hospital, Igando, Lagos State
4. General Hospital, Gbagada, Lagos State
5. General Hospital, Ikorodu, Lagos State
6. General Hospital, Ifako Ijaiye, Lagos State
7. Mother and Child Centre, Gbaja/ Randle General Hospital, Surulere, Lagos State
8. Island Maternity Hospital, Lagos Island, Lagos State
9. Federal Medical Centre, Ebute Metta, Lagos State
10. Ajeromi General Hospital, Ajegunle, Lagos State
11. General Hospital, Isolo, Lagos State
12. General Hospital, Shomolu, Lagos State
13. General Hospital, Orile-Agege, Lagos State
14. Mother and Child, Amuwo-Odofin, Lagos State
15. Obafemi Awolowo University Teaching Hospital, Ile Ife, Osun State.

We have ethical approval to conduct this research in all the hospitals listed above.  We also have Consultant Obstetricians and Gynaecologists, who have keen interest and experience in managing pregnant women with sickle cell disorder, in all the study sites as Site Coordinators.  We have dedicated research nurses, in the employment of each hospital, who will offer you assistance and follow you up all through your pregnancy until you are delivered and discharged from the hospital.

What will be done for me if I join the Trial?

You will first be counseled and, during this process, you will have complete freedom to ask questions and get clarifications.  If you accept to join, you will then sign an agreement form, and subsequently be registered on the trial platform.  All information about you will be kept strictly confidential.

When you join, through a blind process you will be selected into one of two groups – to take low dose aspirin, or not to take (placebo).  Every woman will have a trial drug which either contains low dose aspirin or nothing (placebo) from 16 weeks to 36 weeks of pregnancy or till delivery if they deliver earlier.  They will have some tests done when they register, during pregnancy and at delivery.  Most of these tests are tests often done routinely for women during pregnancy and will all be done free of charge, provided they have to do with the research.  All participants will get messages and/or calls all through pregnancy to remind them to take their drugs and also remind them of their appointments.

What else do I stand to gain from this research?

Your blood level and urine test, which is usually done at every antenatal visit, will be done for you free of charge all through pregnancy.  You will also get your routine drugs, such as Folic Acid, Vitamin B Complex and Proguanil, free all through the pregnancy.

What are my rights during this research?

Participation is voluntary; you may or may not decide to join.  You have a right to request any information about the research that will help you make an informed decision.  Your names and any other identifier will not occur in any publication related to this research.

Will my participation facilitate development in medicine?

Yes!  We strongly believe that the findings of this research will help in improving the quality of care given to women with sickle cell disorder.  It will help us reduce the overall maternal and perinatal deaths that occur worldwide if we find that giving low dose aspirin to all pregnant women with sickle cell disorder offers significant benefit.

For further enquiries or questions, please contact these numbers: 07038090032, 08188339571 or send an email to info@pipsickletrial.com.  You may also follow us on Instagram (@pipsickle2020) and Facebook (PIPSICKLE Trial).

Updates on the PIPSICKLE Trial.

So far, 245 pregnant women with Sickle cell have been enrolled into the trial.  149 of these women have delivered.  We have successfully enrolled almost 50% of the number of pregnant SS or SC women we require.  However, we are still on the lookout for more participants as we need to enroll 478 eligible women in order to hit our sample size target.  Publicity for the PIPSICKLE Trial takes place regularly at the antenatal clinics of the 15 hospitals serving as study sites to the trial, and periodically to the PHCs and other hospitals proximal to the study sites.

Acknowledgement

This research is supported by Tertiary Education Trust Fund (TETFund), Abuja, Nigeria

Appreciations

We are grateful to all the Sickle Cell Clubs across Lagos State for collaborating with us and spreading the messages concerning this research.  We appreciate all Site Coordinators, Research Nurses, Haematologists, Data Officer and all other collaborators for their support.

Conflict of interest

The Authors declare that there is no conflict of interest in conducting this research.

References:

1. Oteng-Ntim E, Ayensah B, Knight M, Howard J. Pregnancy outcome in patients with sickle cell disease in the UK – a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease. Br J Haematol. 2015;169(1):129-37.
2. Villers MS, Jamison MG, De Castro LM, James AH. Morbidity associated with sickle cell disease in pregnancy. Am J Obstet Gynecol. 2008; 199(2):125 e1-5.
3. Obilade OA, Akanmu AS, Broughton Pipkin F, Afolabi BB. Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy. PLoS One. 2017;12(9):e0184345.
4. Lewis DF, Canzoneri BJ, Gu Y, Zhao S, Wang Y. Maternal levels of prostacyclin, thromboxane, ICAM, and VCAM in normal and preeclamptic pregnancies. Am J ReprodImmunol. 2010;64(6):376-83.
5. Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database of Systematic Reviews. 2007.Issue 2. Art. No.:CD004659
6. Moore GS, Allshouse AA, Post AL, Galan HL, Heyborne KD. Early initiation of low-dose aspirin for reduction in preeclampsia risk in high-risk women: a secondary analysis of the MFMU High-Risk Aspirin Study. J Perinatol. 2015;35(5):328-31.
7. Management of Sickle Cell Disease in Pregnancy. Royal College of Obstetricians and Gynaecologists Green-top Guideline. 2011:1-20.
8. Afolabi BB, Iwuala NC, Iwuala IC, Ogedengbe OK. Morbidity and mortality in sickle cell pregnancies in Lagos, Nigeria: a case control study. J Obstet Gynaecol. 2009;29(2):104-6.